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PubMed1994

The effect of previous blood transfusion on lymphocyte subsets and natural killer cell function in patients with colorectal cancer.

To elucidate the possible influence of previous blood transfusion on immune functions, the transfusion history of 153 patients admitted to hospital for elective colorectal surgery was correlated with lymphocyte subsets and natural killer (NK) cell function. The subsets determined were CD2, CD3, CD4, CD8, CD16, CD20, CD56, CD57 and HLA-DR-positive. The NK cell function was determined by measuring the killing capacity against cFDA-labelled K562 target cells monitored via a flow-cytometer. We found that 42 patients (27%) had been transfused before surgery, of these 13 had been transfused less than 30 days before surgery and 29 (19%) transfused more than 30 days before (median 10 years, range 0.1-37 years). In transfused patients, we found a significantly reduced number of B lymphocytes (CD20; p = 0.01), a reduction in HLA-DR-positive cells (p = 0.02) and a just significant reduction of NK cell function in transfused compared to nontransfused patients. The reduction in NK cell function is marginal and the NK cell function is within normal range, and probably without clinical significance. Reduction in NK cell function has been described before, whereas the reduction in B cells has not been reported earlier. The results may suggest an impaired humoral immunity and a minor reduction in cellular immunity in patients following blood transfusion.

Adult↗
PubMed1995

Comparison of blood and synovial fluid lymphocyte subsets in rheumatoid arthritis and osteoarthritis.

Immunoregulatory T-cell deficiency is thought to underlie pathogenesis of rheumatoid arthritis (RA) as a systemic autoimmunopathy. The aim of this study was a simultaneous analysis of peripheral blood and synovial lymphocyte subsets (Ly-SS) of RA patients as compared to patients with locally active osteoarthritis (OA). Peripheral blood Ly-SS and paired synovial fluid Ly-SS from 87 RA patients were analysed by two dimensional flow cytometry (Simulset Becton Dickinson) as compared to 15 OA patients. The control group consisted of 32 healthy subjects. The peripheral blood analysis from RA and OA patients revealed a significant decrease of CD8+ T-cells and increase of CD4+: CD8+ ratio when compared to the control group. The blood of RA patients showed a significant increase of HLA DR+ and IL 2R+ T cells as compared to OA group. The synovial fluid from RA and OA patients showed a significant increase of CD3+, CD8+, HLA DR+ T-cells and decrease of CD4+:CD8+ ratio and CD19+ cells in comparison to the peripheral blood. This study shows, that the OA T-cell system seems not to be activated in peripheral blood in opposition to RA patients. Synovial fluid Ly-SS in OA, however, showed only quantitative but not qualitative differences. OA seems to be mainly a local inflammatory response depending on T-cells, when lymphocyte T activity in blood is diminished.

Aged↗
PubMed1984

Delineation of lymphocyte subsets in lymph nodes of nonhuman primates.

Monoclonal antibodies which recognize specific surface antigens on human lymphocytes were used with an avidin-biotin immunoperoxidase technique to stain lymph nodes from nonhuman primates. Cells in lymph nodes from three macaque species and two new-world primate species could be stained to define T11, T4, T8, and B1 lymphocyte subsets. This approach will facilitate the study of many important spontaneous and experimentally induced diseases of nonhuman primates.

Animals↗
PubMed1988

Virus-lymphocyte interactions. II. Expression of viral sequences during the course of persistent lymphocytic choriomeningitis virus infection and their localization to the L3T4 lymphocyte subset.

Viruses that cause in vivo persistent infections need to selectively compromise the host's immunologic surveillance machinery in order to survive. To understand the molecular basis of how this is accomplished we have analyzed persistent virus infection by lymphocytic choriomeningitis in its normal host, the mouse. Earlier we noted by infectious center analysis that five in 10(4) lymphocytes carried by persistently infected mice contained infectious materials throughout the course of infection. A previous publication extended these results, in BALB mice by showing that the L3T4+ lymphocyte subset in lymph nodes and spleens was predominantly involved. Using cDNA labeled probes to the viral genome and in situ hybridization we report that 1 to 2% of circulating lymphocytes from several mouse strains contain viral RNA sequences for the three viral structural genes. By FACS analysis, the Thy-1.2+, L3T4+ subset primarily harbors virus while viral sequences are usually not detected in the Lyt-2+ subset as early as 6 days after initiating infection in newborns and throughout the course of the persistence. These findings suggest that incomplete, presumably defective, virus is generated in a subset of Th lymphocytes during persistent infection and that during this time infection of cytotoxic T cell subsets is minimal.

Animals↗
PubMed1999

Peripheral lymphocyte subsets and other immune aspects in Rett syndrome.

A possible role of the immune system in the pathogenesis of some neurologic disorders, including infantile autism, was recently postulated. This observation prompted the authors to investigate some immunologic aspects in a group of patients with Rett syndrome, a disorder still not completely clarified but with some points of commonality with infantile autism. Humoral and cell-mediated immunity were investigated in 20 females with Rett syndrome. Peripheral lymphocyte subsets revealed a reduced percentage of CD8+ suppressor-cytotoxic cells in all of the patients with Rett syndrome, resulting in an increased CD4+/CD8+ ratio. In addition, 15 (75%) of the 20 patients had low levels of natural killer cells. Soluble interleukin-2 receptor was elevated in the youngest patients. Antineuronal and antimyelin ganglioside antibodies were absent, as were antinuclear antibodies, antistriated muscle antibodies, and antismooth muscle antibodies. Immunoglobulin fractions and complement were normal for age in all of the patients.

Adolescent↗
PubMed1991

Population dynamics of lymphocyte subsets in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis.

The inflammatory response in the central nervous system (CNS) of rats with differing susceptibility to demyelinating encephalitis induced by coronavirus MHV4 was characterized. Topographical maps showing the arrangement of infiltrating lymphocyte subsets in virus-infected tissue were developed by digital-image processing of immunohistologically stained CNS sections. The kinetics of the inflammatory process was evaluated by flow-cytometry on lymphocytes isolated from the CNS. Cumulative data obtained with these two techniques demonstrated the following features. In susceptible Lewis (LE) rats, viral antigens were disseminated throughout the CNS, including spinal cord. Onset as well as recovery from neurological disease was associated with a steep rise of infiltrating CD8+ T cells, which localized in close contact to virus-infected cells. Accompanying convalescence was a slight increase in B(OX33+) cells in the CNS and the accumulation of immunoglobulin-containing cells in the centre of virus-infected areas. In clinically resistant Brown Norway (BN) rats, virus-infected cells were mainly restricted to small periventricular foci and the extent of lymphocyte infiltration was never as high as that found at any time during the course of infection in LE rats. There were striking differences in the CD8+ T-cell population compared to LE rats. Cells of this phenotype were identified in virus-affected areas of BN rats only early after infection, and their infiltration profile revealed much lower quantities than in the CNS of susceptible LE rats. Although the population dynamics of B(OX33+) lymphocytes were comparable in BN and LE rats, as determined by flow-cytometry, less immunoglobulin-containing B cells were detected in virus-infected areas of BN rats.

Animals↗
PubMed1998

Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal.

To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.

Adolescent↗
PubMed2002

Blood lymphocyte subsets in pigs vaccinated and challenged with Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae bacterins do not induce protection in pigs while infection with low doses of the CM5 strain of A. pleuropneumoniae given by aerosol induces complete protection. To evaluate possible correlates of protection in blood lymphocyte subset phenotypes, pigs were treated with a commercial bacterin given intramuscularly, low dose (10(5)cfu/ml) aerosol infection with CM5 or control treatments of the bacterin adjuvant or phosphate buffered saline. All pigs were challenged with a high dose (10(7)cfu/ml) of A. pleuropneumoniae. Lymphocytes and sera were collected prior to and following primary and secondary immunizations and challenge, for evaluation of B- and T-cell markers and antibody to four A. pleuropneumoniae antigens. IgM(micro)+ B-cells were increased following primary exposure to antigen in the bacterin-vaccinated group only. An increase in CD4+ cells in the LD aerosol-infected group was apparent following secondary exposure to antigen. These early changes suggest little difference in lymphocyte populations between treatment groups, however, greater differences were observed following high-dose challenge; CD4+ lymphocytes were increased significantly in both bacterin and LD-challenged groups (p<0.05) while CD8+ cells decreased in the LD-group at this time period. Consequently, there were significant differences (p<0.05) in the CD4:CD8 ratio after high-dose challenge compared to earlier time points and control groups. Variation in cellular expression of SLA-DR and DQ was observed but trends correlating to treatment group were not evident. Complete protection or lack of protection associated with LD challenge or immunisation resulted in significant differences in B-cell frequencies and CD4:CD8 ratio phenotypes in pigs, but only changes in CD4:CD8 ratios appeared relevant to protection.

Actinobacillus Infections↗
PubMed1990

Analysis of lymphocyte subsets of bone marrow in patients with rheumatoid arthritis by two colour immunofluorescence and flow cytometry.

Lymphocyte subsets defined by monoclonal antibodies were investigated in bone marrow and peripheral blood of 17 patients with rheumatoid arthritis (RA); 13 patients with osteoarthritis or aseptic necrosis served as controls. Patients with RA were found to have a raised OKT 4/8 ratio both in bone marrow and peripheral blood in comparison with the controls. Furthermore, bone marrow of RA showed a lower percentage of OKT 8+ T cells than that of controls. The percentage of HLA-DR+ T cells was higher in bone marrow than in peripheral blood of RA, though a slightly lower percentage was detected in bone marrow than in peripheral blood of controls. Thus T cell subsets in bone marrow of RA differ significantly from those of controls. Patients with RA had a higher OKT 4/8 ratio and a higher percentage of HLA-DR+ T cells in bone marrow than controls, suggesting that T cell subsets in bone marrow of RA are in an immunologically activated state and that T cell subsets are affected by rheumatoid inflammation in bone marrow of RA.

Adult↗
PubMed1996

Prognostic factors of peripheral blood lymphocyte subsets in patients with renal cell carcinoma.

In 76 patients with renal cell carcinoma (RCC) we assessed the therapeutic effects of interferon-alpha (IFN-alpha) and the outcome of curative resection by analyzing changes in peripheral blood lymphocyte subsets to try to find prognostic indices. The percentage of activated CD8-positive cells present in blood samples before IFN-alpha therapy was significantly higher in progressive disease (PD) patients who died within 8 months than in PD patients who survived for more than 18 months. The high percentage of activated CD8-positive cells present in postoperative blood samples was the most remarkable characteristic in patients in which RCC recurred. Multivariate analysis showed that the percentage of activated CD8-positive cells in postoperative blood samples was the only predictor of recurrence (hazard ratio 1.29, p value 0.02). Thus, the high percentage of activated CD8-positive cells in postoperative blood samples is, therefore, a useful indicator of poor prognosis.

Antineoplastic Agents↗
PubMed1992

Bronchoalveolar lavage in alcoholic liver cirrhosis. T-lymphocyte subsets and immunoglobulin concentrations.

The purpose of this study was to determine the phenotype profiles of immune effector cells and the concentrations of immunoglobulins in the lower respiratory tract of non-smoking patients with alcoholic liver cirrhosis (ALC). Nine nonsmoking patients with liver biopsy-proved ALC (grade B or C cirrhosis in Child's classification), free of clinical pulmonary symptoms, and with normal chest roentgenogram were included in the study. The control group included 12 healthy nonsmokers. Each patient had fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The number of T cells and of lymphocyte subpopulations was determined by immunofluorescence studies using monoclonal antibodies that were specific for CD3, CD4, and CD8 markers. Patients with ALC exhibited a dramatically increased percentage of CD8+ cells in BAL that induced a low CD4/CD8 ratio (0.96 +/- 0.15 vs 1.8 +/- 0.12 in healthy controls). Further characterization of lymphocyte subsets' dual immunofluorescence analysis demonstrated that most of the CD8+ alveolar lymphocytes had a phenotype of cytotoxic cells (CD8+ CD11b-; 48 percent +/- 13 in ALC vs 10 percent +/- 5 in controls). ALC was associated with an appreciable alveolar-capillary "leak" as demonstrated by a significant increase in BAL fluid albumin. In addition, the concentrations of immunoglobulins in BAL fluid were significantly greater in ALC than in controls. However, the relative (to albumin) coefficient of excretion of IgG, A, and M in and alpha 2-macroglobulin BAL fluid was not significantly different between controls and ALC. Our results indicate that increased proportions of CB8+ and especially of CD8+ CD11b- cells are a common feature in the lower respiratory tract of nonsmoking patients with ALC. These changes may be of potential functional importance in the regulation of the local pulmonary immune response in ALC.

Adult↗
PubMed1984

T-lymphocyte subset interactions in the cell-mediated immune response to Epstein-Barr virus.

The T-lymphocyte subset interactions in the cell-mediated response to Epstein-Barr virus (EBV) were studied in an in vitro system in which the ability of T lymphocytes to inhibit outgrowth of autologous EBV-transformed B lymphocytes is assessed. Inhibition could be demonstrated within lymphocytes of both the T4 and T8 surface phenotypes. Outgrowth inhibition was observed more frequently when the effector T-cell population contained cells of both surface phenotypes. In blocking experiments the OKT3 antibody completely prevents development of outgrowth inhibitory activity; the OKT4 and OKT8 antibodies were less effective in interfering with outgrowth inhibitory function. Maximal blocking activity occurred when antibody addition occurred in the early phase of generation of suppressor function. Pharmacologically achievable concentrations of interferon-alpha restored outgrowth inhibitory activity after blocking with monoclonal antibody. EBV reactivation was easily demonstrable in a group of 10 renal allograft recipients who received OKT3 antibody for treatment of acute rejection. These studies suggest that the immunoregulatory control of proliferation of EBV-transformed B lymphocytes is complex, and involves a collaborative interaction of lymphocytes of both the T4 and T8 surface phenotypes.

Adult↗
PubMed2001

Sex dependent differences in physiological ageing in the immune system of lower airways in healthy non-smoking volunteers: study of lymphocyte subsets in bronchoalveolar lavage fluid and blood.

BACKGROUND: Age related changes in the immune system have been studied frequently but a possible relation to sex has not, to our knowledge, previously been examined. The effect of age and sex on the composition of lymphocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood was therefore examined. METHODS: Bronchoscopy with lavage was performed in 32 healthy non-atopic, non-smoking volunteers (16 women aged 26-63 years (mean 44) and 16 men aged 23-63 years (mean 39)). Cytospin preparations for differential counts of BAL fluid cells and surface antigen expression of lymphocytes from BAL fluid and blood were analysed by flow cytometry. RESULTS: Most parameters in the BAL fluid changed with age in women. The percentage of CD4+ lymphocytes increased with age from a mean of 48 (SD10)% in women aged < or =40 years to 69 (11)% in women aged >43 years (p=0.001). The percentage of CD8+ lymphocytes tended to decrease with age and the CD4/CD8 ratio was 5.8 (1.2) in women aged >43 years compared with 2.1 (0.7) in those aged < or =40 years (p<0.0001). Women aged >43 years differed from men aged >43 years as well as from younger subjects of both sexes with respect to CD4+ cells and CD4/CD8 ratio, and from younger women with respect to CD8+ cells. There was no age related change in the CD4/CD8 ratio in blood. No sex related differences were seen in the blood or BAL fluid of adults below the age of 40 years. CONCLUSIONS: The composition of lymphocytes with different phenotypes in the lower respiratory tract changes with age in women but not in men. This may have implications for some clinical conditions such as chronic dry cough which are observed predominantly in women.

Adult↗
PubMed1989

The mechanism of the induction of immunologic unresponsiveness to rat cardiac allografts by recipient pretreatment with donor lymphocyte subsets.

In continuation of our studies using UV-B-irradiated DST and donor leukocyte (DL) recipient pretreatment to induce specific unresponsiveness to organ allografts, we have examined the relative contributions of splenic lymphocyte populations and T lymphocyte subsets in the induction of immunologic unresponsiveness. Our data show that enriched populations of MHC class II-positive B lymphocytes and the W3/25+ T cell subset obtained from splenic leukocytes using immunoadsorbent columns in conjunction with mAbs led to indefinite graft survival (greater than 100 days) in the Lewis-to-ACI rat cardiac allograft model. In contrast, pretreatment with T lymphocytes or the Ox8+ T subset was relatively ineffective in prolonging cardiac allograft survival. In addition, third-party (W/F) W3/25+ T cell recipient pretreatment did not influence the survival of Lewis cardiac allografts in ACI recipients, thus confirming the specificity of pretreatment with the T cell subset in graft prolongation. Furthermore, we have examined the underlying mechanisms of donor-specific unresponsiveness induced by donor spleen cells, B lymphocytes, and W3/25+ T cells using adoptive transfer assays. Serial adoptive transfer studies demonstrated the presence of 0x8+ suppressor T cells in the spleens of unresponsive recipients bearing well-functioning cardiac allografts and of serum "suppressor factors" that have the capacity for specifically prolonging donor-type test graft survival in naive syngeneic rats. Our findings suggest that the induction of specific unresponsiveness in this model is dependent on a sequential collaboration between the appearance of donor-specific serum factor(s) (humoral phase) and donor-specific suppressor T cells (cellular phase). These results may be potentially useful in planning future strategies for the induction of unresponsiveness to clinical organ allografts by immunologic manipulation of the host with MHC class II-positive B cell and CD4+ T cell clones.

Animals↗
PubMed1999

Quantitative lymphocyte subset reconstitution after allogeneic hematopoietic transplantation from matched related donors with CD34+ selected PBPC grafts unselected PBPC grafts or BM grafts.

CD34+ cell selection of PBPC after harvest from G-CSF-treated allogeneic donors results in a more than 200-fold depletion of T lymphocytes in the graft and has been used to reduce the incidence of acute GVHD post transplant. Since transplantation with T cell-depleted BM grafts is associated with a delay in immune reconstitution and an increase of opportunistic infections, we evaluated the immunological reconstitution of patients with hematologic malignancies after therapy followed by CD34+-selected PBPC34 transplantation from matched related donors. Lymphocyte subset reconstitution over the first 12 months post transplant and the incidence of infections were evaluated in 12 patients receiving PBPC34 grafts and compared to that of patients after transplantation with PBPC without CD34+ enrichment (n = 20) or unmanipulated bone marrow grafts (BM; n = 15). PBPC34 grafts contained 264-fold fewer T lymphocytes (median 0.53 x 10(6) kg/body weight) than PBPC grafts and 36-fold fewer than BM grafts (140 x 10(6)/kg and 19 x 10(6)/kg, respectively). Despite a two log depletion of T cells in the PBPC34 grafts, T lymphocyte reconstitution appeared comparable among the three transplant groups over the first 12 months. A positive patient CMV serostatus pretransplant was correlated with a faster T cell reconstitution in all transplant groups. GVHD prophylaxis with methylprednisolone delayed B lymphocyte reconstitution. The incidence of infections post transplant did not appear to be increased in the PBPC34 group compared with the PBPC and BMT groups. It remains to be shown in larger prospective trials, whether these promising preliminary data of lymphocyte reconstitution and the clinical course after transplantation with PBPC34 can be confirmed.

Adult↗
PubMed1993

Lymphocyte subsets, sIL2-R and sICAM-1 in blood during allergen challenge tests in asthmatic children.

In order to study cell activation in peripheral blood on bronchial allergen provocation up to 24 h, we investigated 32 asthmatic children, sensitive to house-dust mites. Six healthy young adult volunteers served as controls. Lymphocyte subsets (CD3, CD19, CD4, CD8) and activation markers (CD25-T, HLADR-T, CD23) in peripheral blood as well as soluble IL2-R and soluble ICAM-1 in serum were evaluated. In terms of clinical reaction, 23 children exhibited a DAR, 6 an EAR, 6 a LAR and 3 children did not show a bronchoconstrictor response to allergen challenge with house-dust mite extract (NAR). In comparison to controls, asthmatic children showed a significantly higher expression of CD23 on B-lymphocytes (p < 0.05). Other subsets were in the same range in both groups. After provocation there was a significant increase of CD4/CD8-ratio only in asthmatic children. Serum levels of sIL2-R were significantly higher in asthmatic children compared to controls at baseline as well as at 12 and 24 h after provocation, without variation during observation period. No differences were noted for sICAM-1. Our results confirm the hypothesis that lymphocytes, as important cells in regulation of allergic immune response, are recruited into peripheral blood under allergen challenge conditions in sensitized asthmatic children.

Adolescent↗
PubMedDate not supplied

Effect of intravenous gammaglobulin on organ specific antibodies and lymphocyte subsets.

OBJECTIVE: The intravenous (i.v.) administration of immunoglobulins (Ig) has resulted in clinical improvement and decreased autoantibody titers in a large number of autoimmune diseases. In this study, the in vivo effects of polyvalent Ig for i.v. use (IVIG) on the level and course of organ-specific antibodies and lymphocyte subsets in patients with autoimmune thyroid disease (ATD) were assessed. METHODS: 19 patients were treated with prednisolone (P) while 21 patients received IVIG. Thyroid microsomal, thyroglobulin- and thyrotropin-receptor autoantibodies (Abs), as well as the lymphocyte ratio CD4/CD8, were measured before and at the end of immunosuppressive therapy. RESULTS: Among the patients treated with IVIG, there was a marked decrease (p < 0.0001) in the microsomal, thyroglobulin and TSH-receptor Abs titers. Significant changes in the titers were also observed after P therapy. The lymphocyte ratio dropped markedly in both groups (p < 0.0005). CONCLUSION: The significant decrease in organ specific Abs in the IVIG group may be explained in terms of a direct and local immunosuppressive effect of the drug on the intrathyroid lymphocytes.

Antibody Formation↗
PubMed1984

Analysis with OKT monoclonal antibodies of T-lymphocyte subsets present in blood and liver of patients with chronic active hepatitis.

The relative distribution of T lymphocyte subsets, as defined by the monoclonal antibodies OKT, was determined by cytofluorimetric analysis in peripheral blood and in cells isolated from liver biopsies of 31 patients with chronic active hepatitis (CAH). The percentage of peripheral blood lymphocytes binding OKT8 (directed against cytotoxic/suppressor T cells) was found to be elevated in patients with HBsAg and HBeAg positive chronic active hepatitis. Patients with CAH who had seroconverted to anti-HBe, had an increased number of OKT3-positive cells in their blood, which was directed against a common T cell surface antigen, associated with a decreased number of OKT8 positive cells. Lymphocytes isolated from liver biopsies of patients with CAH presented a general increase of OKT8-positive cells associated with a decreased number of OKT4-positive (helper/inducer) T cells. It is likely that OKT8-positive cells found in liver biopsies represent cytotoxic T cells directed against either viral or liver cell determinants.

Adult↗