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PubMed1992

Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration.

The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Aged↗
PubMed1997

Immunomodulatory effect of beta-carotene on T lymphocyte subsets in patients with resected colonic polyps and cancer.

Results from a number of studies suggest that beta-carotene-containing foods prevent the initiation or progression of various cancers. One possible mechanism for this effect could be enhancement of the immune response. The aim of this study was to determine whether beta-carotene modulates T lymphocyte subsets in patients affected with colonic polyps or cancerous lesions. Patients with previous adenomatous colonic polyps (n = 18) or colon cancers (n = 19) were randomized to receive placebo or beta-carotene (30 mg/day) for three months. Percentages of T lymphocyte subsets were determined using flow cytometry in blood samples collected before randomization and at three months. T lymphocyte subsets of 14 normal control subjects were also determined for comparison. Initially, there was no difference in total leukocyte counts, percentage of lymphocytes, and various subsets of lymphocytes among the three groups, although in cancer patients there was a lower percentage of CD4 and interleukin-2 (IL-2) receptor-positive (IL-2R+) cells than in patients with polyps and in controls. After supplementation with beta-carotene, a significant increase in IL-2R+ T lymphocytes (from 12.7 +/- 3.0% to 26.0 +/- 1.9%) and CD4+ lymphocytes (from 40.9 +/- 3.1% to 45.6 +/- 3.2%) was seen only in the cancer patients. These percentages remained unchanged in patients with adenomatous polyps receiving placebo or beta-carotene. We concluded that beta-carotene increased the number of IL-2R+ T lymphocytes and CD4+ lymphocytes, which in turn may produce IL-2 only in patients with cancer who may already have some deficiency in their immune system. This increase in activated T lymphocytes may mediate cytotoxic reactions to cancer cells via cytokine production.

Adult↗
PubMed1994

Toxoplasma gondii: kinetics of lymphocyte subsets in blood and spleen of perorally infected mice.

The blood and spleen lymphocyte subsets and parasite burdens in blood, lungs, and brain were determined serially in C57B1/6 mice infected with an avirulent strain of Toxoplasma gondii. Five mice were sacrificed at various time points after infection; Thy1-2+, Ly5+, CD4+, CD8+, and Ly6c+ lymphocyte subsets and macrophages were determined in blood and spleen by cytofluorometry and parasite burdens were quantified in blood, lungs, and brain by means of a tissue culture method. In infected mice, a large increase in the percentage of CD8+ lymphocytes in blood was observed from Day 14, peaking at Day 21; the percentage of CD4+ lymphocytes was not significantly modified compared with uninfected controls. Analysis of Ly6 antigen expression on T lymphocytes showed that CD8+Ly6c+ cells were largely predominant at the different stages of infection. Similar results were obtained for spleen cells. The marked increase in CD8+Ly6c+ cells in the early phase of infection was associated with the clearance of parasites from the lungs. Furthermore, the proportion of CD8+Ly-6c+ remained high until Day 162, when the infection was at the chronic stage. These results suggest that CD8+Ly6c+ lymphocytes may be involved in the control of toxoplasmosis in the acute phase and in the containment of the infection in the chronic stage.

Animals↗
PubMed1988

Prognostic value of T lymphocyte subset ratio in idiopathic membranous nephropathy.

The behavior of T lymphocyte subsets was studied in 39 Italian patients with nephrotic syndrome due to idiopathic membranous nephropathy. They took part in a long-term prospective and randomized therapeutic trial based on the 6-month administration of methylprednisolone and chlorambucil. The lymphocyte subsets were evaluated by monoclonal antibodies at the beginning of the trial and at the end of the follow-up period in 23 treated and in 16 untreated patients. Our data seem to suggest that a higher helper-inducer/suppressor-cytotoxic cell ratio before therapy may be a good prognostic index of improved proteinuria. Moreover, the therapeutic schedule does not seem to induce a long-lasting abnormality in cellular immunity.

Adult↗
PubMed1988

Flow-cytometric analysis of lymphocyte subsets in relation to virus infections at the onset of type 1 (insulin-dependent) diabetes.

Alterations in T-lymphocyte subsets have been connected to the autoimmune pathogenesis of Type 1 (insulin-dependent) diabetes. In this study peripheral blood lymphocytes were analysed by flow cytometry using OKT3, OKT4, OKT8, anti-HLA-DR, anti-IL-2 receptor and anti-membrane immunoglobulin antibodies in newly diagnosed Type 1 diabetic children, their healthy siblings and healthy control children. The results were compared to the occurrence of serologically verified recent virus infections, some of which can induce lymphocyte subset alterations and have also been connected with the onset of diabetes. In most diabetic patients the amounts of OKT3, OKT4, OKT8 and membrane-Ig-positive cells were within the normal range. Exceptional helper/inducer and suppressor/cytotoxic T cell profiles were observed in a few patients, most of whom had serologically verified recent Epstein-Barr, rubella, mumps or Coxsackie B virus infection. In addition, increased numbers of activated IL-2 receptor-positive cells were observed in the patient group. These results suggest that significant lymphocyte subset alterations are not characteristic of Type 1 diabetes but can occasionally be induced by recent virus infections in newly diagnosed patients. However, the slight increase in activated lymphocytes could reflect the activation of cellular immune systems to the autoantigens in the pancreas.

Adolescent↗
PubMed1995

Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo.

Lymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well-known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 +/- 5.0% vs. 40.6 +/- 11.0%, T lymphocytes 84.6 +/- 6.3% vs. 56.5 +/- 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 +/- 0.9% vs. 8.9 +/- 3.6%), whereas that in HEV of axLN (19.0 +/- 6.4% vs. 16.6 +/- 6.0%) and PP (30.6 +/- 6.1% vs. 33.9 +/- 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo.

Animals↗
PubMed1984

Peripheral blood T lymphocyte subsets in leprosy.

Peripheral blood T lymphocyte subsets were measured by flow cytometry in 122 patients with leprosy, in 23 normal controls, and in 27 patients with systemic lupus erythematosus (SLE). Active lepromatous patients not in reaction showed a significant lymphopenia and a significant proportionate reduction in the number of OKT3-positive (pan T), OKT4-positive (helper/inducer), and OKT8-positive (suppressor/cytotoxic) cells, but no alteration in distribution as judged by percentage and no abnormality in the helper: suppressor ratio. Borderline lepromatous subjects not in reaction had a significant selective deficiency in the number of cells of the OKT4-positive subset, with a significant but secondary lymphopenia and OKT3-positive cytopenia, a pattern similar to that found in SLE patients. Patients undergoing reversal reactions had a selective deficiency in the OKT4-positive subset in both absolute numbers and as a percentage of total lymphocytes, and a secondary deficiency in the percentage of OKT3-positive cells. No abnormalities were demonstrated in patients with active erythema nodosum leprosum, lepromatous patients with long-term treatment, and untreated or treated borderline tuberculoid patients.

Humans↗
PubMed1985

Variables affecting T-lymphocyte subsets in a volunteer blood donor population.

Inversion of the normal ratio of helper/inducer (Th) to suppressor/cytotoxic (Ts) T lymphocytes is a characteristic finding in symptomatic and presymptomatic patients with acquired immunodeficiency syndrome (AIDS). As an interim measure to prevent transmission of AIDS via blood transfusion, the Stanford Blood Center performed T-lymphocyte subset analysis as a screening procedure. In this report we present results from 8715 consecutive volunteer blood donors, aged 17-77. The mean Th:Ts ratio was 2.00 +/- 0.70 with a significant trend for increasing Th:Ts with increasing age. In all age groups, donors with antibody to cytomegalovirus (CMV) had lower Th:Ts ratios than CMV-seronegative donors. 1.9% of the donors had Th:Ts values less than or equal to 0.85 and blood from these donors was not used for clinical purposes. Compared to the overall donor population, individuals with Th:Ts less than or equal to 0.85 tended to be male, (79 vs 53%) and CMV sero-positive (71 vs 36%); a majority (83%) had a low absolute number of Th cells as well as a low Th:Ts value. Follow-up of donors with low Th:Ts values revealed that some belonged to AIDS high-risk populations, despite denials at the time of donation. One such donor was diagnosed with disseminated Kaposi's sarcoma 8 months after a markedly abnormal T-lymphocyte subset profile was noted during screening. These results suggest that T-lymphocyte subset analysis is capable of identifying at least some blood donors at risk for transmitting AIDS and also point to variable affecting T-cell subsets in apparently healthy blood donors.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Long-term evolution of lymphocytes subsets after induction therapy based on continuous versus discontinuous administration of anti-thymocyte globulins in renal-transplant patients.

UNLABELLED: The aim of our retrospective study was to assess the long-term evolution of lymphocyte subsets after two modes of administration of anti-thymocyte globulin (ATG) after renal transplantation. METHODS: Before 1993, patients (group I, n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until the serum creatinine level became <150 micromol/L. After 1993, patients (group II, n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and, thereafter, doses were adapted to target a CD2 T-cell count <50/mm3. RATG cumulative dose was significantly higher among group I than group II (9.7 +/- 4.5 versus 7.4 +/- 3.2 mg/kg, P = .0002). RESULTS: In both groups, total lymphocyte and T lymphocyte subset (CD4, CD8, CD2, CD3) counts decreased significantly during the first month after transplantation, increasing slowly between the first month and the third year posttransplantation. Thereafter it rose rapidly, which was greater in group II. At last follow up, total lymphocyte, T lymphocyte subsets and NK cell counts were similar to those observed before transplantation. At all monitoring times, T lymphocyte, B lymphocyte, and NK cell counts were similar in both group, except for the total lymphocyte count at 6 months and CD4 T lymphocyte count at 1 year, which were significantly higher in group II compared to group I. CONCLUSION: Induction therapy based on continuous or discontinuous administration of ATG is associated with profound depletion of T, B, and NK cells during the first 3 years, followed by a progressive reconstitution of the lymphocyte pool after 5 years.

Antigens, CD↗
PubMed1993

Influence of stress on lymphocyte subset distribution--a flow cytometric study in young student pilots.

Stressors can induce sizable modifications on immunocompetent cells. Major circulating lymphocyte subsets were quantitated in Italian Air Force student pilots undergoing intensive training and continuous evaluation, a stressful situation both physically and psychologically. Instructor pilots matched for age and assayed in parallel were used as controls. A typical flight training session was not able per se to induce immediate significant modifications of the lymphocyte subset distribution either in the students or instructors, although it did affect plasma levels of stress-related hormones such as growth hormone, prolactin and cortisol in the former. Irrespective of the time of flying, however, the percentage of CD4+ lymphocytes and the CD4/CD8 ratio were lower in students than in instructors, and the absolute number of CD8+ lymphocytes was higher in students than in instructors. In a second series of experiments, 30 student pilots were tested at the beginning and at the end of a flight course (duration 30 days). Although the percentage of CD29+ lymphocytes comprised in the CD8+ subset was reduced at the end of the course in all individuals, such a reduction was more evident in those students who failed to pass the final examination, an additional cause of psychological stress. In light of the functional significance of the lymphocyte subsets investigated, it is suggested that the present stress-induced alterations may have practical implications.

Adult↗
PubMed1991

Classic Kaposi's sarcoma: T-lymphocyte subsets, T4/T8 ratio, and NK cell activity.

Lymphocyte function as expressed by T-lymphocyte subsets and natural killer cell activity was evaluated in a group of Israeli patients with classic Kaposi's sarcoma. T-cell subsets were examined in 28 patients, 14 with lesions limited to the lower extremities and 14 with diffuse cutaneous or systemic involvement. CD4 and CD8 lymphocytes and CD4/CD8 ratio were in the normal range in all patients, and mean values of the entire group were similar to a control group. However, CD8 was in the upper limits of the normal range in some patients with diffuse cutaneous or systemic involvement. This factor led to a significantly decreased CD4/CD8 ratio in that group as compared with the group of patients with the disease limited to the lower extremities. Mean values of natural killer cell activity in three effector/target cell ratios were significantly decreased in 13 of the patients with Kaposi's sarcoma with lesions limited to the lower extremities and in all of the patients with normal T-cell subsets and CD4/CD8 ratios.

Adult↗
PubMed1988

Lymphocyte subset distribution and natural killer activity in growth hormone deficiency before and during short-term treatment with growth hormone releasing hormone.

Natural killer (NK) cell activity was assessed in the peripheral blood of 20 patients with growth hormone (GH) deficiency due to a hypothalamic deficit of GH-releasing hormone (GHRH). All patients failed to respond to at least two provocative tests of GH secretion (GH below 7 ng/ml) but responded to a single GHRH iv bolus injection (1 microgram/kg body wt). In 14 of the 20 patients (20 determinations), lymphocyte subsets were also measured; in all patients the distribution of lymphocyte subsets was within the normal range. More importantly, NK cell activity in the 20 patients was significantly lower than in controls (P less than 0.01). To assess the in vivo effect of GH and GHRH on NK activity and lymphocyte subset distribution, immunologic tests were performed (i) before and after a single iv bolus injection of GHRH (1 microgram/kg body wt) in six patients; (ii) before and after 3 weeks of GHRH treatment (3-9 micrograms/kg body wt, one to four times daily) in five patients; and (iii) after 6 weeks of GH treatment (5 IU sc every alternate day) in one patient. Neither NK activity nor the distribution of lymphocyte subsets was altered during short-term GHRH administration. In conclusion, low NK activity is found in GH-deficient patients, and short-term administration of GH or GHRH fails to restore this immunological abnormality. This result suggests that the hypothalamus may be a regulator of NK activity in the human and that patients with hypothalamic deficiencies should be monitored for the development of discrete immunodeficiencies.

Adolescent↗
PubMed2005

The selective expression of distinct fucosylated glycoproteins on murine T and B lymphocyte subsets.

The putative expression of distinct terminally fucosylated glycoconjugates among murine lymphocyte subpopulations was sought using Ulex europaeus agglutinin-I (UEA-I) and Anguilla anguilla agglutinin (AAA), each with a distinctive primary binding preference to type II and type I blood group H oligosaccharide determinants, respectively. In newly born and adult mice, direct labeling of isolated lymphocyte subsets in suspension, as well as immunohistochemical assays were indicative of the age-regulated co-expression of the UEA-I-reactive ligand among thymic epithelial cells and a subset of the mature (PNA-), medullary thymocytes. In the spleen, UEA-I-ligand expression was selectively confined to a subset of the CD4+ T lymphocytes scattered around red pulp sinuses in newly born mice, but distinctively localized within the T cell-dependent periarteriolar lymphoid sheath compartment in adult mice. Among thymocytes of adult mice, two-dimensional Western blots demonstrated the expression of the UEA-I-reactive ligand among multiple isoforms of three major 50, 114 and 180kDa acidic glycoproteins, of which, heterogeneous weight and charge variants of the 114kDa component were also evident among splenocytes. The expression of the AAA-reactive ligand was, on the other hand, restricted to a single major 120 kDa acidic glycoprotein, in addition to a minor molecular weight variant of 115kDa, associated with a subset of immature IgM+ B lymphocytes localized within the red pulp, in both newly born and adult mice. The significance of these findings is discussed in relation to mechanisms that govern lymphocyte maturation, selection and migration.

Anguilla↗
PubMed1987

Altered lymphocyte subsets during cardiopulmonary bypass.

Peripheral blood lymphocyte subsets were quantified by immunofluorescence in nine patients undergoing open heart surgery for coronary artery, valvular, and congenital heart disease. Compared with normal preoperative values, all patients developed an absolute lymphopenia, a reduction in T4 (helper) lymphocytes, and a statistically significant reversal of the T4/T8 ratio two hours after cardiopulmonary bypass (CPB). These changes could be caused by mechanical or immunogenic injury. A return to normal of the T4 subset and T4/T8 proportion occurred 24 hours after surgery. Whereas transient inactivation of immunoreactive lymphocyte clones may prevent unwanted immunization to blood products received during surgery, such temporary immune dysfunction could make certain patients liable to infectious sequelae. Viral-induced postperfusion syndromes, transmission of human T lymphotropic virus (HTLV) III by blood products, and reports of acquired immune deficiency syndrome after CPB foster a concern regarding postoperative infections under these circumstances.

Adult↗
PubMed2000

Use of mRNA differential display to study the action of lymphocyte subsets in vivo and application to a murine model of herpes simplex virus infection.

Depletion of lymphocyte subsets in vivo using monoclonal antibodies against cell surface markers has helped to define the roles for these subsets in many immune processes. However, in some cases the mechanisms through which these lymphocytes act remain partially elucidated or completely unknown. A new approach to these biological problems is the use of transcriptional analyses to find mRNAs whose abundance in tissues is altered by depletion of lymphocyte subsets. We have verified the use mRNA differential display (DD) for this purpose and applied it in a study of CD8(+) lymphocyte mediated clearance of herpes simplex virus (HSV) from the nervous systems of experimentally infected mice. The results of the differential displays and characterisation of a large mRNA identified using this strategy are presented.

Animals↗
PubMed1996

CD8 lymphocyte subsets in active polymyalgia rheumatica: comparison with elderly-onset and adult rheumatoid arthritis and influence of prednisone therapy.

The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.

Age of Onset↗
PubMed1999

Longitudinal study of lymphocyte subsets and major histocompatibility complex-class II expressing cells in mammary glands of sows.

OBJECTIVE: To determine whether there is variation attributable to reproductive stage in lymphocyte subsets and major histocompatibility complex (MHC) class II expressing cells in mammary glands of sows. ANIMALS: 8 healthy primiparous crossbred sows that had been nursing piglets for 30 to 35 days. PROCEDURE: Needle biopsy of the mammary gland was performed after parturition, at midlactation, and after weaning. Various lymphocyte subsets and MHC class II expressing cells were detected immunohistochemically, using monoclonal antibodies. RESULTS: The number of CD8+ cells was significantly lower after parturition than after weaning but not significantly lower than at midlactation. The number of IgA-bearing cells was lower after parturition and after weaning than at midlactation. There were more B cells at midlactation than after weaning. There was no change over time in the number of CD4+ cells or MHC class II expressing cells. Immunohistochemically positive cells were detected only in interalveolar tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Certain lymphocyte subsets in mammary glands of sows are affected by reproductive stage. The data do not support the hypothesis that development of postparturient coliform mastitis may be the result of impaired mammary immune defenses at parturition.

Animals↗
PubMed1991

Lymphocyte subsets in Eastern Highlanders of Papua New Guinea.

Lymphocyte subsets were enumerated in Papua New Guinean children, adolescents and adults from the Eastern Highlands and comparative groups of age-matched expatriates living in the Goroka area. From the age group under 6 months until adolescence, the numbers and percentages of CD8-positive (suppressor/cytotoxic) T cells were higher in Papua New Guinean highlanders than in expatriates. In highland subjects over 35 years of age, both CD8-positive and CD4-positive (helper/inducer) T-cell numbers were lower than in younger subjects whereas in expatriates their numbers remained the same. Highlanders over the age of 35 years had fewer T cells (including CD8-positive T cells) than expatriates. Helper/suppressor ratios were lower in highlanders than in expatriates from the age group under 6 months to the 20-30 year age group; the lowest ratio was found at 10-15 years of age, when the mean was 0.95.

Adolescent↗