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PubMed2001

Morphological study of erythrocyte shapes in red pulp of mouse spleens revealed by an in vivo cryotechnique.

The purpose of this study was to clarify erythrocyte shapes in splenic cords of living mouse spleens, using our in vivo cryotechnique followed by scanning (SEM) or transmission (TEM) electron microscopy. Some spleens of mice were quickly frozen by the in vivo cryotechnique while their hearts were beating under anesthesia. In contrast, other spleens were prepared by an in vitro freezing method after they were taken out from the abdominal cavity. They were routinely freeze-substituted, and prepared for SEM and TEM. A few mouse spleens were also routinely fixed and embedded in Quetol-812 to obtain conventional morphology. Erythrocytes in living mouse spleens showed a variety of shapes with narrow spaces between them, trapped among reticular fiber tissues. Similar various shapes of erythrocytes were kept in the red pulp even after blocking normal blood circulation, as prepared by the in vitro freezing method. In comparison to the above-mentioned findings, some erythrocytes were changed to biconcave discoid shapes by the conventional immersion fixation with chemical fixatives. They also showed wide spaces between each other among reticular fiber tissues. Such conventional morphological studies could hardly reveal the in vivo shapes of erythrocytes in functioning spleens with normal blood circulation. In contrast, the various shapes of erythrocytes in the functioning spleens were demonstrated by our in vivo cryotechnique. It is suggested that most erythrocytes congesting in spleens keep their original configuration in spite of microenviromental alteration in splenic blood circulation.

Animals↗
PubMed2003

Adjuvant cytokine treatment of minimal residual disease after surgical therapy in mice carrying HPV16-associated tumours: cytolytic activity of spleen cells from tumour regressors.

It has been found previously that IL-2, IFNgamma and GM-CSF were capable of reducing the recurrence rate of HPV 16-associated tumours in mice with SMRTD. We were interested whether the therapeutic effect of the surgery and adjuvant cytokine treatment was accompanied by cytolytic activity of spleen cells and whether the activity of the spleen cells was different in mice that had rejected tumour residua after surgery and adjuvant therapy with cytokines (tumour regressors) as compared to those that had not rejected the tumour residua (tumour progressors). We have examined the cytolytic activity of spleen cells from MHC class I+ TC-1 tumour regressors and progressors after treatment of TC-1 SMRTD with GM-CSF, and the activity of spleen cells from MHC class I- MK16 tumour regressors and progressors after treatment of MK16 SMRTD with IL-2 and IFNgamma. It has been found that irrespective of the tumour type and adjuvant treatment, the spleen cells from tumour regressors after surgery were regularly more cytolytic when allowed to react with target cells from HPV 16-associated tumours than the spleen cells from tumour progressors. No substantial differences between the cytolytic activity of spleen cells from the operated-only and operated plus cytokine (GM-CSF, IL-2, IFNgamma) adjuvant treated groups were observed. The cytolytic activity of spleen cells from mice with SMRTD allowed to react with MHC class I+ , MHC class I-, NK-sensitive and NK-resistant targets is compatible with the interpretation that in the mice with MHC class I+ TC-1 tumours, primarily cytotoxic T lymphocytes (CTL) were efficient, whereas in the mice with MHC class I- MK16 tumours, both NK and non-lymphocytic effector cells were involved.

Animals↗
PubMedDate not supplied

[The weight of the spleen in chronic chagasics].

During the course of systemic inflammatory reactions and chronic venous congestion, the documented phenomenon of increased spleen size is respectively called reactional hyperplasia and congestive splenomegaly. In Chagas' disease, the inflammatory process observed in the heart of chronically infected patients can result in heart failure and ultimately in congestive failure. In order to evaluate the spleen response to both inflammatory and cardiac processes, in this retrospective study we compare the weight of spleens from normal and chagasic patients, with or without congestive failure. Information about patient age, sex, race and spleen weight was collected from autopsy reports. Eighty-eight selected cases were divided into four groups: 1) chagasic patients with congestive failure, 2) chagasic patients without congestive failure, 3) non-chagasic patients with congestive failure, 4) non-chagasic patients without congestive failure. The average age was 44.9 +/- 15.4 years, 53.4% were Caucasians and 70.5% were males, and no significant difference in these parameters was observed between the four groups. The spleen weight for the groups presenting congestive failure was 183.7 +/- 85.9 g for chagasic and 206.3 +/- 101.0 g for non-chagasic patients; for the groups without congestive failure the average spleen weight was 173.7 +/- 118.9 g for the chagasic and 117.2 +/- 52.0 g for non-chagasic patients. The spleen weight was significantly higher for the chagasic patients without congestive failure when compared to the non-chagasic group without congestive failure. These results suggest that the inflammatory component in Chagas' disease plays an important role in the increase of spleen weight together with hemodynamic alterations arising from congestive heart failure.

Adult↗
PubMed2002

The human spleen during physiological stress.

Many mammals have the ability to autotransfuse a large quantity of red blood cells from the spleen into the active circulation during times of stress. This enhancement of the oxygen transport system has benefited the athletic mammal, that is, the thoroughbred horse, fox and greyhound in an improved aerobic performance. The role of the spleen in sequestering 50% of the total red cell volume in seals and horses, during times of inactivity, dramatically reduces the viscosity of the blood and therefore the work of the heart. In comparison, the human spleen contains only a small percentage of red blood cells, and has been primarily thought of as a lymphoid organ. The aim of this review is to emphasise the similarities between the human spleen and that of several athletic mammalian species during acute physiological stress. In the athletic mammalian model the expulsion of blood from the spleen is facilitated via the sympathetic nervous system resulting in contraction of smooth muscle within the splenic capsule. In comparison, the lack of smooth muscle contained within the human splenic capsule has meant that active contraction of the spleen has historically been viewed as unlikely, although evidence of contractile proteins within the red pulp have suggested otherwise. Exercise results in haemoconcentration, which has been attributed solely to a reduction in plasma volume. Indirect calculation of plasma volume changes utilise haemoglobin and haematocrit and assume that the circulating red cell volume remains constant. However, several studies have suggested that the human spleen could account for 30% of the increase in haematocrit. This would result in a substantial overestimation of the reduction in plasma volume, indicating that the expulsion of red blood cells from the spleen must not be overlooked when utilising these equations.

Animals↗
PubMed1999

Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse.

The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue-specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell-Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system.

Animals↗
PubMed1975

[Experimental and clinical results of autotransplantation of part of the spleen].

Eleven patients with traumatic rupture of the spleen were subjected to splenectomy and autotransplantation of part of the spleen. The technique of the operation is described: 5--20% of the spleen is incised into transversal slices of 2--3 mm of thickness which are placed along the periphery of omentum majus, they are enveloped in it and are studied. The number of the applied transplants is 3--6. By means of hematological tests the authors prove that the transplants have functions close to those of the spleen. The clinical and laboratory investigations have revealed that in 9 of the patients operated no symptoms of asplenia were present, whereas in another two patients signs of hyposplenism were detected. Immune studies have demonstrated that no autoimmune reactions have followed autotransplantation of part of the spleen. The indications for the operation are mentioned: traumatic rupture of the spleen, benign tumours and cysts of the spleen with splenic parenchyme being preserved. Contraindications for autotransplantation of part of the spleen are all cases with the syndrome of hypersplenism and systemic blood disorders--lymphogranulomatosis, leucemia, reticuloses and others.

Adult↗
PubMed2000

[MRI of the spleen].

PURPOSE: The aim of this study is to show the possibilities of MRI in diagnostic of the spleen affections. MATERIAL AND METHODS: During a two years period, MRI of the splen alone was performed in 13 patients, while MRI of the liver was performed in 213 patients. With the liver, we examined the spleen as well. Using 1.0T Unit (Siemens Magnetom Impact) we performed next sequences: T1W SE, T2W TSE FS, PD T2W, with and without breath hold. Rutinly we used body coil. We divided all patients in two groups: 1st group--13 patients undergoing spleen examination, and 2nd group--213 patients with liver and spleen examination with retrospective analysis. RESULTS: In the first group--10 patients, MRI of the spleen provided us with some new information compared with CT and US. In three patient there were no new diagnostic information. In second group, accidently showed cystic postraumatic lesions, there was trombotic aneurysm of the lienal artery. Also in the patients with liver disease spelnomegaly was found in 25. DISCUSSION: According to the literature and our initial experience, MRI of the spleen is not yet in wide clinical practice because of the little difference of the relaxation time of the spleen and proton density. Introducing of the paramagnetic contrast media will provide increasing of abilities in the detection of the tumor lesion. Further development advances towards diagnostic of the lymphatic infiltration, staging of metastatic carcinoma, and differential diagnostic of splenomegaly. CONCLUSION: According to our experience and literature, MRI of the spleen is not yet in wide clinical practice, for now.

Female↗
PubMedDate not supplied

Detection of early gamma-postirradiation effects in murine spleen by proton NMR relaxation times.

BACKGROUND: It was our aim to evaluate the potential of proton relaxation times for the early detection of radiation-induced spleen changes. MATERIALS AND METHODS: Female Swiss mice were irradiated with doses ranging from 0.05 Gy to 4 Gy. The body weight, the spleen weight and the spleen water content of single animals were determined. Measurements of longitudinal (T1) and transversal (T2) proton relaxation times of the spleen samples were performed in a 0.47 T spectrometer. Histological examinations of the control and irradiated organs were performed. RESULTS: NMR measurements during the first five days after irradiation showed that total body gamma-irradiation with doses from 1.5 Gy to 4 Gy results in decreasing T1 of the murine spleen. Significant shortening in T2 was observed for the spleen of animals irradiated with a dose of 4 Gy. Histological examinations demonstrated subnormal architecture in slices derived from animals irradiated with 2 Gy and 4 Gy. CONCLUSION: The fluctuations of the spleen T1 and T2 of irradiated mice are correlated with relative spleen weight and can be used to estimate radiation induced changes in this organ.

Animals↗
PubMed1976

Effect of altered lighting regimens, time-limited feeding, and presence of Ehrlich ascites carcinoma on the circadian rhythm in DNA synthesis of mouse spleen.

The objectives of the series of experiments described were (a) to determine whether there was a circadian rhythm in the incorporation of tritiated thymidine into DNA of the spleen in mice kept on a conventional light-dark cycle and fed ad libitum, (b) to study the effect that different light-dark cycles and a time-limited feeding schedule had on this circadian rhythm, (c) to ascertain what effect the presence of an 8-day Ehrlich ascites carcinoma (EAC) had on the rhythm in DNA synthesis in the spleen and what effect the EAC had on the circadian rhythm in the mitotic index in the corneal epithelium, and (d) to determine whether there was a circadian rhythm in the duration of life-span in mice bearing the EAC. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse spleen consistently was characterized by a peak during the nocturnal phase and a trough during the diurnal phase of the 12-hr light-12-hr dark cycle. In animals bearing an 8-day EAC, the rhythm in DNA synthesis in the spleen was phase-shifted, its wave form was changed, and the overall 24-hr mean was increased significantly. The phasing of the rhythm in EAC-bearing mice was not reproducible. This finding demonstrated that the presence of the EAC severely altered the natural rhythm in DNA synthesis in the spleen and resulted in a rhythmic pattern which was constantly changing. The presence of an 8-day EAC, however, had no effect on the amplitude, overall level, or the phasing of the circadian rhythm in the mitotic index in the cornea. A staggered light-dark cycle of 2 weeks duration did not completely phase-shift the DNA synthesis rhythm in the spleen but did completely phase-shift the rhythm in the mitotic index in the corneal epithelium. In mice subjected to a daily feeding period limited to 4 hr, the rhythm in DNA synthesis in the spleen, in both EAC-bearing and non-EAC bearing mice, was phase-shifted such that the peak occurred during the time of feeding and the trough occurred prior to the feeding period. The rhythm in the mitotic index in the cornea was not phase-shifted or altered in any way by the feeding schedule and thus remained fixed to the light-dark cycle. The DNA synthesis rhythm in the normal spleen demonstrated a phasing very similar to the circadian rhythm in the length of survival in mice challenged with EAC and the circadian rhythm in DNA synthesis in the normal thymus.

Animals↗
PubMedDate not supplied

Population dynamics of natural killer cells and T lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: the effect of indomethacin.

Quantitative and functional methods were used to assess changes in NK (ASGM-1+, nonblast, lymphoid) cells and cytotoxic/suppressor T (Lyt-2+) cells in the spleen and bone marrow (BM) of normal DBA/2 mice and/or mice bearing early (7 days)- and late (14 days)-stage erythroleukemia +/- concomitant oral administration of indomethacin. In normal mice, indomethacin increased ASGM-1+ cells in the spleen and BM by 7 days of continuous drug administration relative to control, while the numbers of Lyt-2+ cells in both organs remained unaltered. The presence of a tumor in untreated mice resulted, by 14 days development, in elevated numbers of ASGM-1+ cells in the spleen and BM. Lyt-2+ cells in the spleen increased transiently (7 days) in tumor-bearing (TB) mice and returned to normal levels by 14 days TB. No difference in either early- or late-stage TB was observed in the numbers of Lyt-2+ cells in the BM. In spleen and BM of TB mice, indomethacin increased ASGM-1+ cells by 7 days TB. ASGM-1+ cells returned to untreated levels by 14 days TB in both organs in spite of continued drug treatment. The numbers of Lyt-2+ cells in both the spleen and BM of 7 days indomethacin-treated TB mice were reduced relative to those of untreated TB mice. By 14 days TB, drug treatment had no effect on Lyt-2+ cell numbers in the spleen or BM. Spontaneous cytolytic activity of the spleen and BM did not always parallel changes in the numbers of ASGM-1+ cells, indicating the presence of late, immature, prelytic NK cells among the ASGM-1+ cell numbers. The results demonstrate that the numbers of NK and cytotoxic/suppressor T cells are markedly but differentially affected during tumor growth and/or time of exposure to indomethacin in an organ-specific manner.

Animals↗
PubMed1992

Leukaemia and anaemia in AKR/O mice. II. Role of the spleen as an erythropoietic organ during leukaemia development.

In order to study the role of the spleen in erythropoiesis during AKR/O leukaemogenesis, we have cultured bone marrow and spleen erythroid colony-forming units (CFU-E) and burst-forming units (BFU-E) from AKR/O mice (n = 40) with leukemia of varying severity and type of manifestation. Mice with leukaemia/lymphoma had reduced concentrations of bone marrow CFU-E and BFU-E as compared to healthy, age-matched AKR/O mice. The spleen content of CFU-E was increased, and highest in mice with a spleen size between 500 and 1000 mg. The largest spleens had a somewhat lower CFU-E content. Mice with the highest spleen CFU-E content most often had a normal PCV; however, 4/7 had a normal bone marrow CFU-E concentration. During AKR/O leukaemogenesis with development of spleen enlargement, the spleen may act as an erythropoietic organ, and contribute to maintaining a normal PCV. This may be a temporary ability which is reduced or lost with further progress of the disease.

Anemia↗
PubMed2004

Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells.

AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism. METHODS: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-gamma, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method. Effects of ginsenoside-F3 on mRNA level of cytokines IL-4, IFN-gamma, and transcription factors T-bet and GATA-3 were evaluated by RT-PCR analysis. Effect of ginsenoside-F3 on NF-kappaB DNA binding activity in murine spleen cells was investigated by electrophoretic mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100 micromol/L not only promoted the murine spleen cell proliferation, but also increased the production of IL-2 and IFN-gamma, while decreased the production of IL-4 and IL-10 from murine spleen cells with the maximal effect at 10 micromol/L. RT-PCR analysis displayed that ginsenoside-F3 enhanced the IFN-gamma and T-bet gene expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed that ginsenoside-F3 10 micromol/L enhanced the NF-kappaB DNA binding activity induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1 cytokines and type 2 cytokines in murine spleen cells.

Animals↗
PubMed2005

A quantitative ultrastructural study of the liver and the spleen in fatal falciparum malaria.

We performed a retrospective study of 25 patients who died of severe falciparum malaria in Thailand and Vietnam using electron microscopy. The aims of the study were: to determine if there was any significant association between parasitized red blood cells (PRBC) sequestered in liver and spleen and particular pre-mortem clinical complications, and to compare the degree of parasite load between the liver and spleen within the same patients. PRBC sequestrations in each organ were compared with the pre-mortem parasitemia, to calculate the sequestration index (S.I.). The S.I. showed that the degree of PRBC sequestration in the spleen was higher than the liver (S.I. median = 3.13, 0.87, respectively) (p < 0.05). The results of quantitative ultrastructural study showed a significantly high parasite load in the liver of patients with jaundice, hepatomegaly and liver enzyme elevation (p < 0.05). We found a significant correlation between PRBC sequestration in the liver and a high serum bilirubin level, a high aspartate aminotransferase (AST) level and an increase in the size of the liver (Spearman's correlation coefficient = 0.688, 0.572, 0.736, respectively). Furthermore, a higher parasite load was found in the liver of patients with acute renal failure (ARF) compared to patients without ARF (p < 0.05). These findings suggest that PRBC sequestration in the liver is quantitatively associated with pre-mortem hepatic dysfunction and renal impairment. There was no significant difference between splenomegaly and PRBC sequestration. The size of a palpable spleen was not correlated with parasite load in the spleen. When ultrastructural features were compared between the two reticuloendothelial organs, we found that the spleen had more PRBC and phagocytes than the liver. The spleen of non-cerebral malaria (NCM) patients had more phagocytes than cerebral malaria (CM) patients. This observation reveals that the spleen plays a major role in malaria parasite clearance, and is associated with host defence mechanisms against malaria.

Adolescent↗
PubMed2006

Focal lesions in the ultrasonographic examination of the spleen as a symptom of various disease statuses: literature survey and case descriptions.

BACKGROUND: Ultrasonography (US) is an easy and non-invasive technique of visualizing spleen. Thanks to its repeatability, it plays an important role in the diagnostics of, among others, developmental anomalies, such as supernumerary or lobated spleens, as well as focal lesions. It is also used in monitoring the size of the spleen and it considerably facilitates diagnosis after certain injuries. Thanks to the application of the Doppler method, it also facilitates the diagnostics of pathologies within the spleen's vessels. CASE REPORT: This paper presents six different cases of focal lesions in the spleen, including lesions in the course of histiocytosis, in the course of sarcoidosis, as well as isolated abscesses of the spleen. The authors also present the case of a spleen with numerous metastatic lesions, the case of a near-splenic cyst, and the case of asymptomatic focal lesions of unknown origin. In all the presented cases, the lesions were accidentally revealed during ultrasonographic examination, which was the starting point for further diagnostics. CONCLUSIONS: Though rare, morphologic lesions in the spleen should always be taken into consideration when performing a routine ultrasonographic examination of the abdominal cavity, and the organ itself should not be ignored. US is a widely available, noninvasive, and useful method for diagnosing splenic abnormalities, including focal changes.

Adolescent↗
PubMed2006

Effect of immunotherapy and spleen preservation on immunological function in patients with gastric cancer.

Splenectomy is often performed in patients who undergo total gastrectomy for cancer of the upper stomach. Although splenectomy facilitates lymph node dissection of the splenic hilum and recent reports advocate spleen preservation, the role of the spleen is not fully elucidated in gastric cancer treatment. This prospective randomized study was performed to evaluate the role of the spleen in immunological function in gastric cancer patients who underwent total gastrectomy and received postoperative immunochemotherapy. Forty-five patients with gastric cancer were randomly allocated to four groups: 1. splenectomy without immunotherapy (OK-432 administration), 2. splenectomy with immunotherapy, 3. spleen preservation without immunotherapy, 4. spleen preservation with immunotherapy. Postoperative immunological function of these patients was compared among the four groups. NK cell activity of the peripheral blood lymphocytes (PBL) in spleen-preserved patients who received immunotherapy was significantly higher for 24 weeks after surgery than that of the splenectomized patients with and without OK-432 administration. IL-2 production of PBL in spleen-preserved patients with immunotherapy was significantly higher between 4 and 24 weeks after surgery compared with that of the splenectomized patients without immunotherapy. The results suggest that spleen preservation might be beneficial in patients with less advanced gastric cancer who receive postoperative immunochemotherapy after total gastrectomy.

Adenocarcinoma↗
PubMed1986

Regulation of immune responses by T cell subsets. Role of helper and suppressor T cells in the development and expression of MHC-restricted antibody responses to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by (responder X responder)F1 spleen cells.

The roles of helper and suppressor T cells in the development and expression of antibody responses to GAT were studied in (responder X responder)F1 mice immunized with parental GAT-M phi. Spleen cells from (B10 X B10.D2)F1 mice primed in vivo with B10 or B10.D2 GAT-M phi developed secondary in vitro plaque-forming cell (PFC) responses only when stimulated by GAT-M phi syngeneic with the GAT-M phi used for in vivo priming. By contrast, virgin F1 spleen cells developed comparable primary PFC responses to both parental GAT-M phi Co-culture of T cells from (B10 X B10.D2)F1 mice primed in vivo by B10 GAT-M phi with virgin (B10 X B10.D2)F1 spleen cells demonstrated the presence of suppressor cells that inhibited the primary response of virgin spleen cells stimulated by B10.D2 GAT-M phi. Spleen cells from (B10 X B10.D2)F1 mice primed in vivo with B10.D2 GAT-M phi had suppressor T cells that suppressed primary responses stimulated by B10 GAT-M phi. The suppressor T cell mechanism was composed of at least two regulatory T cell subsets. Suppressor-inducer T cells were Lyt-2-, I-J+ and must be derived from immune spleen cells. Suppressor-effector T cells can be derived from virgin or immune spleens and were Lyt-2+ cells. When the suppressor mechanism was disabled by treatment with 1000 rad gamma irradiation or removal of Lyt-2+ cells, Lyt-2-helper T cells from (B10 X B10.D2)F1 mice primed with B10 GAT-M phi provided radioresistant help to virgin F1 B cells stimulated by B10 but not B10.D2 GAT-M phi. Suppressor inducer Lyt-2-,I-J+ cells from B10 GAT-M phi-primed (B10 X B10.D2)F1 mice were separated from the primed Lyt-2-,I-J-helper T cells. In the presence of Lyt-2+ suppressor effector cells, the Lyt-2-,I-J+ suppressor-inducer suppressed the primary response of virgin spleen or virgin T plus B cells stimulated by both B10 and B10.D2 GAT-M phi. Therefore, suppressor T cells were able to suppress primary but not secondary GAT-specific PFC responses stimulated by either parental GAT-M phi. These results showed that immunization of (responder X responder)F1 mice with parental GAT-M phi results in the development of antigen-specific helper and suppressor T cells. The primed helper T cells were radioresistant and were genetically restricted to interact with GAT in association with the major histocompatibility complex antigens of the M phi used for in vivo priming.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent-strain spleen cells. II. Evidence for an Hh-1 antigen-specific tolerization.

Lethally irradiated F1 mice reject bone marrow graft from H-2b parents. In a previous paper we showed that pretreatment of F1 hybrid with H-2b parental spleen cells abrogates this hybrid resistance (HR) to parental bone marrow growth by inducing a Thy-1+Lyt-1+2- nylon-adherent suppressor cell. We studied the mechanism of induction of this suppressor cell. Two hypotheses were tested; both were based on the observation that parental spleen cells when injected into a F1 hybrid, recognize the alloantigens of the opposite parent and proliferate; the proliferation of these Hh-1+ cells may result in an overload of the pretreated F1 hybrids with Hh-1 Ag, and in the development of a graft-vs-host reaction that is followed by a non-specific immunodeficiency (GVHID). Thus abrogation of HR could be due to either a tolerization with high doses of Hh-1 Ag or the GVHID. Our results show that abrogation of HR does not correlate with the GVHID because 1) it is induced after pre-treatment with H-2b parental cells only, whereas GVHID is observed after injection with cells from either of the two parents; and 2) it is induced in several conditions where GVHID does not occur; after pre-treatment with 1000-rad-irradiated or T-cell depleted or only class I incompatible spleen cells or with spleen cells from nude parents as well as after pre-treatment with H-2b bone marrow cells. HR is overcome by the injection of H-2Db homozygous or of cross-reactive H-2Ds homozygous cells only. However, although pretreatment with H-2Db homozygous spleen cells is necessary, it is not sufficient for an efficient overcoming of HR. Indeed enhancement of H-2b bone marrow growth after pre-treatment with 1000-rad-irradiated, T-cell depleted or nude parent spleen cells is very short-lasting and never reaches the level observed after pre-treatment with normal spleen cells. We conclude that inhibition of HR in F1 hybrids pretreated with parental spleen cells is not a consequence of a GVHID but of a specific tolerization with Hh-1 Ag; however, the HR is inhibited more consistently when inoculum used for the pretreatment contains fully immunocompetent T cells. The role of the immunocompetent parental T cells in abrogation of HR is discussed.

Animals↗
PubMed1986

Frequent T4-positive cells with cytolytic activity in spleens of patients with Hodgkin's disease (a clonal analysis).

Purified T lymphocytes isolated from spleens of untreated patients with Hodgkin's disease (HD) were cloned by using a microculture system previously shown to allow clonal expansion of virtually all peripheral blood T lymphocytes. Cells were plated under limiting conditions with irradiated feeder cells and PHA. Interleukin 2 (IL 2)-containing supernatants were added 48 hr later. The phenotypic and functional characteristics of a total number of 221 clones derived from six different HD spleens were investigated and compared with those of 133 clones obtained from three spleens of otherwise healthy individuals who underwent posttraumatic splenectomy. The majority of T cell clones derived from HD spleens expressed the T4+ (helper/inducer) phenotype. However, further functional characterization showed that as much as 50% of these T4+ clones displayed cytolytic activity in a lectin-dependent lytic assay allowing detection of cytolytic cells of any specificity. In contrast, less than 10% T4+ clones derived from control spleens were cytolytic, as assessed by the same lectin-dependent lytic assay. The cytolytic potential of T4+ and T8+ clones established from spleens of patients with HD did not reflect the induction of lymphokine-activated killer cells, because only a minority of them displayed natural killer (NK) activity against NK-sensitive K562 and MOLT-4 cell lines. These findings indicate that T lymphocytes found in the spleens of patients with HD may represent, at least in part, the expansion of a subset present in small percentages among normal peripheral blood or spleen T lymphocytes, which is involved in a cytotoxic reaction.

Antigens, Differentiation, T-Lymphocyte↗