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PubMed2004

Dynamics of CD62L/CD45RB CD4+ and CD8+ lymphocyte subsets in hepatic and splenic tissues during murine visceral leishmaniasis.

This study aimed to characterise, for the first time, the dynamics of CD4+ and CD8+ lymphocyte CD62L/CD45RB subsets, during visceral leishmaniasis. Memory/activated status of hepatic and splenic T cells was compared in mice strains with "cure" and "non-cure" phenotypes to Leishmania infantum infection. In both mice strains, a correlation between the dynamics of the memory CD4+ and CD8+ T cells (CD62Llow/CD45RBlow) subsets in the liver and the pre-activated phenotype of lymphocytes (CD62Llow/CD45RBhigh) from the spleen was detected suggesting that this organ is the source of Leishmania-specific T lymphocytes that migrate to the liver, where parasite replication is highly active. In the liver, these pre-activated cells become effector T lymphocytes, however, a strong regulation of CD8+ T cell effector function was observed, probably preventing hepatic tissue damage. Comparing mice strains with "cure" and "non-cure" phenotype, an imbalance between "protective" CD45RBhigh and "pathogenic" CD45RBlow CD4+ subsets in B10.D2/n animals might be involved in the evolution of a non-healing infection.

Animals↗
PubMed1997

Effect of long-term platelet donation on lymphocyte subsets and plasma protein concentrations.

Previous studies of changes in immune function in platelet donors have investigated subjects who were undergoing plateletpheresis using older equipment that is no longer in general use. Therefore, the purpose of this study was to determine the effect of long-term platelet donation on lymphocyte numbers and subsets and plasma protein concentrations in platelet donors using newer cell separators. Three groups included in the study were nondonor controls (n = 27), long-term whole blood donors (n = 29), and long-term platelet donors (n = 20). Using a cross-sectional analysis, lymphocyte numbers and subsets were determined and compared among the three groups. Plasma concentrations of total protein, globulin, albumin, and IgG were also compared. Among the three groups there were no significant differences in total white blood cell counts, percentage or absolute number of lymphocytes, or percentage or absolute number of lymphocyte subsets. Serum total protein, globulin, albumin, and IgG concentrations of platelet donors were within normal ranges. These data support the current Food and Drug Administration (FDA) and American Association of Blood Banks' standards for the frequency of platelet donation allowed and monitoring required for plateletpheresis donors. Furthermore, these data indicate that the FDA could eliminate the requirement for the warning in informed consents about lymphocyte depletion in platelet donors.

Adult↗
PubMed1999

Kinetics of the changes of lymphocyte subsets defined by cytokine production at single cell level during highly active antiretroviral therapy for HIV-1 infection.

The effects of highly active antiretroviral therapy on cytokine imbalances associated with HIV-1 infection have not been characterized. Using single cell analysis by flow cytometry, we show that a significant recovery in the frequency of IL-2-producing cells was only observed in patients with a sustained control of viral replication and that the overexpanded CD8 T cell population of CD28- IFN-gamma + cells was not significantly reduced after 1 yr of effective therapy. Moreover, a detrimental role of IL-4 is suggested by the association between an enhanced proportion of IL-4-producing cells within the CD4 and particularly the CD8 subset and viral load rebound. Finally, the kinetics of changes of cell subsets assessed for simultaneous production of different cytokines supports the view that cell reconstitution during highly active antiretroviral therapy is initially due to redistribution of terminally differentiated cells, followed by peripheral expansion of less differentiated ones and a late progressive increase of the proportion of functionally defined naive/memory precursor lymphocytes. These data bring new support for the role of cytokine imbalances in AIDS pathogenesis and may be relevant for the definition of immunointervention targets.

Adult↗
PubMed1992

Differential function of intestinal intraepithelial lymphocyte subsets.

It has been proposed that intestinal intraepithelial lymphocytes (I-IEL) perform immune surveillance of the epithelial layer (1) and regulate mucosal humoral responses to exogenous Ag (2). To better understand the functional potential of this unique population, purified murine I-IEL were analyzed phenotypically and functionally. Initial studies determined that I-IEL could be distinguished based on several phenotypic characteristics including: TCR (TCR-alpha beta vs TCR-gamma delta); Thy-1, CD45R/B220, CD5, and CD8 (CD8 alpha alpha vs CD8 alpha beta) expression. Using anti-TCR mAb, individual I-IEL subsets were activated and examined functionally. Both TCR-alpha beta and TCR-gamma delta I-IEL were found to synthesize an array of lymphokines that included IL-2, IL-3, and IL-6 but not IL-4 or IL-5. Additionally, a number of lymphokines were detected that directly influence epithelial function (IFN-gamma, TNF-alpha, and TGF-beta 1). However, the majority of the I-IEL function was localized within the Thy-1+, CD45R/B220- I-IEL subset. In addition those TCR-alpha beta I-IEL expressing the CD8 alpha beta heterodimer were more easily activated. Thus, a subset of I-IEL have the capacity to respond to TCR-mediated stimuli. The functional activities of these cells may influence both local immune cell populations as well as epithelial differentiation.

Animals↗
PubMed2002

Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats.

The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2-28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5(+)-CD4(+) T cells, MHC class II(+) cells, or ED1(+) macrophages. However, the percentage of CD5(+)-CD8(+) T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0-28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.

Animals↗
PubMed1979

Characterization of thymus-derived lymphocyte subsets in acute Epstein-Barr virus-induced infectious mononucleosis.

Changes in thymus-derived (T) lymphocyte subpopulation numbers were studied in patients with acute and convalescent Epstein-Barr virus (EBV)-induced infectious mononucleosis (LM). T cell subsets were characterized by the presence of Fc receptors for IgG (TG), for IgM (TM) or by the absence of either receptor (Tnon-M, non-G). We found that in acute IM, total numbers of T and B lymphocytes were elevated (p less than 0.01). Of the T lymphocyte subsets, the total number of Tnon-M, non-G lymphocytes was increased six fold compared to normal subjects (p less than 0.001) and included the majority of the atypical T lymphocytes. The number of total TG and TM lymphocytes was moderately increased (p less than 0.05). In convalescent IM patients, the number of total T cells remained slightly elevated (p less than 0.02) whereas proportions and absolute numbers of B lymphocytes and T cell subsets returned to near normal levels. Thus, acute Epstein-Barr virus-induced IM is associated with a T lymphocytosis which is composed predominantly of atypical T cells which lack detectable Fc receptors for IgG or IgM.

Acute Disease↗
PubMed2005

Discovering lymphocyte subsets.

At a scientific meeting in 1968, Jacques Miller was accused of complicating immunology. He and others suggested that there was not one but two kinds of lymphocytes--one from the thymus and one from the bone marrow. In a pair of groundbreaking articles published in the Journal of Experimental Medicine in 1968, Miller and his student Graham Mitchell proved that two subsets of lymphocytes did exist and identified which subset mediated antibody responses.

Allergy and Immunology↗
PubMed1987

Functional properties of CD8 positive lymphocyte subsets in systemic lupus erythematosus.

CD8+ lymphocytes comprise several cell subpopulations that differ phenotypically and functionally. Although the percentage of T cytotoxic/suppressor cells (CD3+ CD8+) is usually increased in patients with active SLE, these lymphocytes are unable to suppress immunoglobulin (Ig) synthesis. However, freshly prepared lymphocytes from patients with SLE contain CD8+ DR+ cells which spontaneously suppress lymphocyte production of mitogen induced interleukin 2 (IL-2). Furthermore, CD8+ Leu 11+ non-T cells which comprise only 5% of total lymphocytes are also potent suppressors of IL-2 production. At the present time it is not known whether CD8+ suppressors of Ig synthesis and CD8+ suppressors of IL-2 production represent different maturation stages of common precursor cells or represent true heterogeneity of CD8+ lymphocytes.

Humans↗
PubMed1994

Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C.

Longitudinal changes in lymphocyte subpopulations, including total and activated T cells, B cells, and NK cells as well as NK activity and 2',5'-oligoadenylate synthetase (2'5' AS) levels were determined in peripheral blood before, during, and after therapy with human recombinant interferon-alpha (HurIFN-alpha) in 39 patients with serologically and biopsy-confirmed chronic hepatitis C. Immunologic data obtained at baseline and during IFN-alpha administration were correlated with the clinical response to IFN-alpha therapy defined as a normalization of the serum alanine aminotransferase level. There were 23 responders (R) and 13 nonresponders (NR) to IFN-alpha and 3 patients were not evaluable. Prior to the use of IFN-alpha, the patients tended to have higher numbers of activated (DR+) T and NK cells but a lower number of CD3+CD25+ T cells than normal controls. During IFN-alpha therapy, highly significant induction of 2'5'AS was observed. The numbers of circulating WBC, total lymphocytes, and T and B cells were reduced during IFN-alpha therapy. In contrast, both the absolute number and percentage of activated CD3+CD25+ and CD4+DR+ T cells increased in response to the IFN-alpha therapy. The percentage of activated CD56+DR+ NK cells was also significantly elevated over the pretreatment baseline. IFN-alpha therapy had no effect on NK activity in peripheral blood mononuclear cells. No differences in the immunologic profile of R vs NR were noted, except that the number of IL2R+ T cells was increased transiently early during IFN-alpha therapy but only in the NR group. It was not possible to reliably discriminate between R vs NR to IFN-alpha therapy on the basis of longitudinal changes in the phenotype or function of immune effector cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

The correlation of Epstein-Barr virus expression and lymphocyte subsets with the clinical presentation of nodular sclerosing Hodgkin disease.

BACKGROUND: The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocytes in HD and its relations to clinical presentation and to EBV expression have not been characterized fully. Grade II HD is a more aggressive form of the disease. The authors studied cases of HD by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph nodes and to characterize the phenotype of these lymphocytes in relation to EBV expression, tumor grade, and clinical presentation. MATERIALS AND METHODS The authors prospectively studied lymph nodes from 48 patients with the diagnosis of HD by FCM for T (CD3, CD4, and CD8) and B (CD19) lymphocytes. Ratios of helper to suppressor (CD4 to CD8) and ratios of T to B (CD3 to CD19) lymphocytes were calculated. In situ hybridization for EBV also was performed. The tumors were graded. Clinical data related to age and stage of the disease were retrospectively analyzed. RESULTS: There were 30 male and 18 female patients with an age range of 7 to 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Eleven (23%) cases were classified as Grade II disease. All Grade II cases showed EBV expression, whereas only 13 (39%) cases of Grade I disease were positive (P = 0.03). EBV-positive cases had a median CD4 to CD8 ratio of 1.62, whereas EBV-negative cases had a ratio of 3.86 (P = 0.01). Grade I cases had a median CD4 to CD8 ratio of 4.58, whereas Grade II cases had a ratio of 1.62 (P = 0.007). EBV-positive cases had a median T-lymphocyte to B-lymphocyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.77). Grade I cases had a median T-lymphocyte to B-lymphocyte ratio of 3.51, whereas Grade II cases had a ratio of 1.71 (P = 0.001). A higher percentage of children was seen in the EBV-positive cases than in the negative ones (58% vs. 29%). Cases with low (< 1.5) CD4 to CD8 ratios showed more incidence of high-stage disease (Stages III and IV) than patients with higher ratios (81% vs. 51%). High-stage disease also was seen more frequently in patients with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%). CONCLUSION: The authors found that the local immune response in HD may vary from one case to another. The findings also suggest that EBV may play a role in the pathogenesis of the disease in relation to T- and B-lymphocyte response. A more profound immune suppression and decrease in overall T and helper lymphocytes may be seen in aggressive EBV-positive variants of the disease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior.

Adolescent↗
PubMed1995

Effect of surface antigen-1 (SA-1) immune lymphocyte subsets and naive cell subsets in protecting scid mice from initial and persistent infection with Cryptosporidium parvum.

We tested the hypothesis that adoptive transfer of immune spleen cell subsets from Cryptosporidium parvum antigen immunized, immunocompetent BALB/c mice would prevent initial infection or terminate persistent infection in severe combined immunodeficient (scid) mice. Cell donor mice were immunized with either solubilized C. parvum oocysts and sporozoites (positive control) or a surface antigen-1 (SA-1) enriched C. parvum antigen fraction. Both groups of BALB/c cell donor mice immunized with C. parvum antigens had increased antibody titers and lymphoproliferative responses when compared with negative control mice injected with phosphate buffered saline and adjuvant. Intravenous adoptive transfer of 5 x 10(6) cells of each cell subset (spleen cells, CD4 T and B lymphocytes, CD4 T lymphocytes or B lymphocytes) derived from immunized adult BALB/c donor mice did not protect scid mice against initial infection of the gastrointestinal epithelium with C. parvum, despite flow cytometric evidence of CD4 T lymphocyte engraftment in the spleen and detectable levels of C. parvum-specific serum antibody. In contrast, intravenous injection of either naive or immune CD4 T and B lymphocytes combined, or CD4 T lymphocytes alone, terminated persistent C. parvum infection in scid mice. Intestinal infectivity scores were significantly reduced by 9 days post-engraftment in all groups and continued to decline throughout the remainder of the experiment. Flow cytometric analysis demonstrated significantly increased CD4 T lymphocytes in the spleens of recipient scid mice when compared with infected scid mice receiving no cells. Cryptosporidium parvum-specific antibody was detected on day 12 post engraftment in mice receiving SA-1 immune CD4 T and B lymphocytes but was not detectable in mice receiving naive cell subsets.

Animals↗
PubMed1989

Intraepithelial T-lymphocyte subsets in the airways of normal subjects and of patients with chronic bronchitis.

Lymphocyte infiltration of central airway epithelium was evaluated in 13 normal nonsmoking subjects (Group 1), in 11 smokers without clinical signs of chronic bronchitis (Group 2), and in 34 patients who were smokers with chronic bronchitis and mild airflow limitation (Group 3). Bronchial samples were obtained through fiberoptic bronchoscopy. Murine monoclonal antibodies directed against cell-surface antigens and an immunoperoxidase technique were used on cryostat sections to label in situ the following lymphocyte populations: T-lymphocytes (CD3+), helper/inducer T-cells (CD4+), suppressor/cytotoxic T-cells (CD8+) and B-lymphocytes (leu 12+). Virtually no B-cells were found in central airway epithelium from subjects of any group. Conversely, consistent infiltration of epithelial layers with T-lymphocytes of both subsets was observed in all subjects, with a constant predominance of CD8+ over CD4+ cells. For any T-cell marker, differences between mean scores from Group 1 and Group 2 subjects were not statistically significant. On the other hand, mean lymphocyte numbers of both subsets were found increased in patients from Group 3 compared with subjects from the two other groups: statistically significant differences were observed for CD3+, CD4+, and CD8+ cells (p less than 0.001). Furthermore, lymphocyte scores at two different airway generation were compared in some patients from Groups 2 and 3, and a significant positive correlation was observed. These results suggest that T-lymphocyte infiltration of central airway epithelium (1) may be a naturally occurring phenomenon that is amplified in the airways of smokers with chronic bronchitis, and (2) may represent the counterpart to the intraepithelial population of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Two-color immunofluorescence and flow cytometric analysis of peripheral blood lymphocyte subsets in Caucasian and Japanese healthy subjects.

Two-color immunofluorescence using multiparameter flow cytometry was employed to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of healthy Caucasians and Japanese. The CD4/CD8 ratio in Japanese was significantly decreased compared with that in Caucasians, because of the increased number of CD8+ cells. Although the proportions of suppressor-inducer T cells (CD4+, Leu-8+) and helper-inducer T cells (naive T cells) (CD4+, CD45RA-) were low in Japanese subjects, there were no differences in the absolute numbers of suppressor-inducer T cells and helper-inducer T cells (naive T cells) in circulation. The level of activated T cells in Japanese was similar to that in Caucasians. NK cells, CD57+, CD8+ cells and CD57+, CD3+ cells were high in Japanese. Regarding B cell subsets, CD5+ B cells and activated B cells remained unchanged. However, there were slight differences in Leu-8+ B cells and Fc epsilon R+ B cells (CD20+, CD23+) between the two groups. Thus, a differing influence of racial and environmental background between healthy Caucasians and healthy Japanese on human lymphocyte subsets is present in the lymphocyte immunophenotype.

Adult↗
PubMed2007

Identification of a novel CD160+ CD4+ T-lymphocyte subset in the skin: a possible role for CD160 in skin inflammation.

CD160 is a glycosylphosphatidylinositol-anchored cell surface molecule expressed by human circulating cytotoxic lymphocytes that correspond to the majority of natural killer cell (NK) expressing CD56(dim), TCRgammadelta lymphocytes, and to a minor CD8 T-cell subset. CD160 engagement by major histocompatibility complex class I molecules triggers by itself both cytotoxic function and cytokine production in NK lymphocytes, whereas it provides co-activating signals to TCR-induced proliferation in T CD8+ lymphocytes. In this study, we analyzed by immunohistochemistry the phenotype of lymphocytes infiltrating normal skin and inflammatory skin lesions of atopic dermatitis, contact dermatitis, and psoriasis. We identified a minor original subset of CD4+ CD160+ T cells infiltrating inflammatory lesions. We found that this lymphocyte subset localization is not restricted to the skin, as we demonstrated that CD160 transcripts could be induced in IL-2 or IL-15-activated CD4+ peripheral blood lymphocytes. Finally, we report that CD160 acts as a co-activator receptor for CD3-induced proliferation of CD4+ CD160+ T cells isolated from inflammatory skin lesions. Thus, we hypothesize that the unique CD4+ CD160+ lymphocyte subset plays a role in the pathogenesis of skin inflammation.

Adolescent↗
PubMedDate not supplied

B cells and T-lymphocyte subsets of the head-associated lymphoid tissues of the chicken.

The head-associated lymphoid tissues of the chicken, composed of the harderian gland and the conjunctiva-associated lymphoid tissue (CALT), were studied to determine whether changes occurred in lymphocyte subpopulations as chickens age from 1 week to 8 weeks. The B cells and subpopulations of T-lymphocytes of the head-associated lymphoid tissues were identified using in situ immunohistochemical staining. Monoclonal antibodies specific for various lymphocyte surface antigens were used. The concentration of T-lymphocytes, particularly CD3+ and CD4+ cells, within the harderian gland increased with age, whereas the concentration of B cells remained the same. B-lymphocytes were observed within the germinal centers of the CALT of 4-week-old birds. The T-lymphocytes within the CALT surrounded the B-cell-rich germinal centers. CD3+ T-lymphocytes were the predominant cell population in all age groups examined. Increasing concentrations of CD3+, CD4+, and CD8+ T-lymphocytes were observed within the CALT as chicks developed from 1 week to 4 weeks of age. Finally, no changes were observed in lymphocyte populations within the CALT as chicks developed from 4 weeks to 8 weeks of age.

Aging↗
PubMed1998

Characterization of lymphocytes in the adult rat testis by flow cytometry: effects of activin and transforming growth factor beta on lymphocyte subsets in vitro.

The rat testis is considered to be an immunologically privileged site because of its reduced capacity to support antigen-specific immune responses. To understand this phenomenon, it is essential to characterize both the lymphocyte subpopulations normally present in the testis and their regulation by testicular cytokines. Peripheral blood was obtained from adult male Dark Agouti or Sprague-Dawley rats, and testicular interstitial tissue was collected after perfusion of the testes to remove blood. Blood and testis lymphocytes were isolated using discontinuous Percoll density gradients, and the testicular lymphocytes were further purified by selective adherence to remove mononuclear phagocytes. The isolated lymphocytes were analyzed by flow cytometry using specific monoclonal antibodies and fluorescein labeling and were enumerated as total T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells. In contrast to peripheral blood, in which the CD4+ T-cell subset was the major lymphocyte subset, rat testis T cells were predominantly of the CD8+ subset, and a large population of NK cells also were present. Subsequently, peripheral blood lymphocytes were stimulated with the polyclonal T-cell activator, phytohemagglutinin, and cultured in the presence of activin, inhibin, or transforming growth factor beta (TGFbeta) prior to flow cytometric analysis. Activin and TGFbeta suppressed T-cell proliferation without any selective effect on either T-cell subset, and inhibin had no effect. The predominance of CD8+ T cells and NK cells, and the relatively minor proportion of CD4+ T cells, are consistent with both increased cellular immune surveillance and a reduced capacity for initiating antigen-specific immune responses in the adult rat testis.

Activins↗
PubMed1999

[Analyze T lymphocyte subsets of HIV/AIDS patients by flowcytometer].

OBJECTIVE: Using flowcytometer (FCM) to detect CD4+, CD8+ lymphocytes in peripheral blood, combine with clinical symptoms to evaluate the HIV/AIDS patients' immune state. METHODS: Anti-coagulated peripheral blood were obtained from 8 HIV-AIDS patients and 5 normal persons. After analyzing their total white cell counts, the whole blood was stained with two-color immunofluorescence using directly conjugated monoclonal antibody pairs, followed by lysis of red erythrocytes, fixation of lymphocytes, and analysis by flowcytometry. Multiplying the CD4 and CD8 percentages by the absolute number of lymphocytes obtained from the total white blood cell (WBC) count divide by the lymphocyte differential percentage, we got the CD4, CD8 counts. RESULTS: The HIV/AIDS patients' CD4 counts were lower than those of normal controls'. Especially, the AIDS patients' CD4 counts were all below 200 cells/mm3 and their clinical symptoms were serious. CONCLUSION: The HIV/AIDS patients' CD4 counts are highly correlated with their clinical symptoms. The result also shows that FCM is accurate, sensitive and reliable in CD4 count.

Acquired Immunodeficiency Syndrome↗