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Results for “CD8+ T cells”

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At least 19 recordsLinked to original sources

PubMed1992

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.

Adult↗

PubMed2026

Plasma cell-CD8+ T cell co-enrichment distinguishes immunotherapy-responsive hepatocellular carcinoma subtypes.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterised by significant racial disparities in incidence and outcomes, yet whether these reflect distinct tumour biology or differential distribution of molecular subtypes among immunotherapy patients remains unclear. METHODS: We characterised molecular heterogeneity among 46 patients with HCC of differing background population from the NCI-CLARITY cohort receiving immune checkpoint inhibitor therapy, using transcriptomic and genomic profiling, with validation across multiple independent cohorts. RESULTS: Differential expression analysis comparing African American versus non-African American patients identified 126 genes, of which 55 demonstrated tumour-specific expression across independent validation cohorts with paired tumour-normal samples. Consensus clustering revealed two molecular subtypes with no significant race association, indicating these clusters capture tumour-intrinsic biology rather than ancestry. The genomic landscape showed minimal differences between subtypes. A prognostic signature derived from these expression profiles demonstrated significant risk stratification in the NCI-CLARITY cohort and TCGA-LIHC, but not in Asian cohorts, suggesting population-specific applicability. Immune deconvolution revealed that the two subtypes represent distinct immune microenvironments: one subtype exhibited markedly elevated plasma cell infiltration with strong plasma cell-CD8+T cell correlation suggesting coordinated adaptive immunity, along with elevated tertiary lymphoid structure signatures. The other subtype showed regulatory T cell-macrophage correlation and enrichment for immune-excluded phenotypes. The immune-enriched subtype trended towards higher immunotherapy response rates. CONCLUSIONS: Molecular heterogeneity in HCC reveals distinct tumour-immune ecosystems that transcend racial classification. Tumour immune heterogeneity in HCC reflects distinct molecular patterns, with immune hot tumours characterised by elevated tertiary lymphoid structure signatures and enriched plasma cell and CD8+T cells. These patterns may serve as prognostic biomarkers for immunotherapy patient stratification and demonstrate the value of diverse cohort representation in identifying clinically relevant therapeutic targets.

Gastrointestinal Cancer↗

PubMed1992

Suppression of spontaneous murine lupus by inducing graft-versus-host reaction with CD8+ cells.

Splenic CD8+ (Lyt-2+) cells of C57BL/6 mice were injected into semiallogeneic (NZB x BXSB)F1 mice, which spontaneously develop lupus nephritis, in order to examine whether the disease was somehow modified by the occurrence of graft-versus-host reaction. The development of lupus nephritis in the F1 recipients was strongly inhibited and immunopathological parameters such as anti-DNA antibodies, circulating immune complexes (CIC) and splenic immunoglobulin-producing cells (IgPC) were markedly reduced. The injection of CD4+ (L3T4+) T cells into F1 recipients did not result in similar effects. These findings suggest that the development of autoimmune disease could be ameliorated by CD8+ cells responding to MHC class I antigens. The significance of the data is discussed in terms of the treatment of autoimmune diseases.

Animals↗

PubMed1992

HIV-1 expression in chimpanzees can be activated by CD8+ cell depletion or CMV infection.

CD8+ cell antiviral activity and cytomegalovirus (CMV) were investigated in vivo as possible cofactors influencing the outcome of HIV-1 infection. The role of CD8+ cell suppression of HIV replication was evaluated by depleting CD8+ cells in two infected chimpanzees by inoculation with monoclonal anti-CD8 antibodies. Two other infected animals were injected with chimpanzee CMV (CCMV)-infected human fibroblasts to determine if exposure to this virus would induce HIV replication. Treatment with anti-CD8 antibody resulted in recovery of virus from the CD4+ lymphocytes of one animal at 1, 4, and 6 months, and from a second animal at 1 month postinoculation. In contrast, virus had been recovered only once or not at all from these infected chimpanzees for 4 years prior to treatment. Similarly, HIV was recovered from the CD4+ cells of the two animals 2 to 3 months after inoculation of CCMV-infected fibroblasts but not after inoculation of control uninfected fibroblasts. These studies suggest that CD8+ cell-mediated suppression and the presence of other viruses (such as CMV) could act as cofactors in influencing the extent of HIV-1 replication in vivo and, possibly, progression to disease.

Animals↗

PubMed1992

Anti-CD3-induced T-cell activation in vivo--I. Flow cytometric analysis of dose-responsive, time-dependent, and cyclosporin A-sensitive parameters of CD4+ and CD8+ cells from the draining lymph nodes of C57Bl/6 mice.

An in vivo model to assess the effects of chemicals on T-cell activation has been characterized and validated using the immunosuppressive drug, cyclosporin A (CsA). The dose response and kinetic effects of the hamster anti-mouse monoclonal antibody 145-2C11 (anti-CD3) on various parameters of T-cell activation were examined in cells from the draining popliteal and inguinal lymph nodes of C57Bl/6 mice. Parameters of anti-CD3-induced T-cell activation included 3H-TdR incorporation (+/- recombinant murine IL-2), and flow cytometric analysis of CD3 and IL-2 receptor (IL-2R) expression on CD4+ and CD8+ cells. Increases in the percentage of lymphocyte subsets in the S/G2M phase of the cell cycle and total cell recovery following anti-CD3 are also reported. Increased 3H-TdR incorporation was maximal over a dose range of 0.25-25 micrograms anti-CD3, while maximal increases in the percentage of CD4+ and CD8+ cycling occurred after a dose of 2.5 micrograms anti-CD3. At 24 h after anti-CD3 treatment, CD3 expression on both CD4+ and CD8+ cells was dose dependently down-modulated while IL-2R expression and IL-2-driven 3H-TdR incorporation were dose dependently increased. In addition, total cell recovery increased at 24 h and correlated with an increase in the percentage of B220+ cells present in the lymph nodes. There was a corresponding decrease in the percentage of Thy 1.2+, CD4+, and CD8+ cells. No increase in cycling of B220+ cells was observed, suggesting an influx of B220+ cells into the node rather than proliferation. Elevation in 3H-TdR incorporation occurred as early as 4 h after anti-CD3 treatment, while increases in the percentage of CD4+ and CD8+ cells cycling were not apparent until 24 h. At 48 h, the percentage of CD8+ cells cycling doubled while the percentage of CD4+ cells cycling remained constant. Down-modulation of CD3 expression on CD4+ and CD8+ cells was apparent as early as 1 h after treatment with less than 10% of CD4+ and CD8+ cells expressing CD3 by 12 h. Induction of IL-2R expression and IL-2-driven 3H-TdR incorporation was maximal at 12 h after anti-CD3. The immunosuppressive drug, CsA (25, 50, or 100 mg/kg, i.p.) decreased anti-CD3-induced 3H-TdR incorporation. Concurrently, anti-CD3-induced increases in the percentage of CD4+ and CD8+ cells cycling were inhibited by CsA. Likewise, IL-2 responsiveness and IL-2R expression on both T-cell subsets were inhibited by CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Phenotypic and functional characteristics of activated CD8+ cells: a CD11b-CD28- subset mediates noncytolytic functional suppression.

Freshly isolated human CD8+ cells can be divided into mutually exclusive subsets bearing the phenotypes CD11b+(CD28-) or CD28+(CD11b-). We found that activation of CD8+ cells with anti-CD3 mAb and IL-2 preferentially expanded the CD11b-(CD28+) subset. This subset, when separated and activated independently, mediated both functional suppression and lectin-dependent cell cytotoxicity (LDCC). CD28- cells, prepared by elimination of the CD 28+ cells from expanded unfractionated CD8+ cell cultures, retained functional suppressor activity but demonstrated reduced LDCC compared to either the CD28+(CD11b-)-enriched fraction or the unfractionated CD8+ population. The majority of the CD28- cells were also CD11b-, reflecting the observation that initially CD11b+ cells lose CD11b expression following activation with anti-CD3 mAb and IL-2. Our results therefore indicate that CD8+ cells deriving from the CD11b+CD28- subset, but expressing neither CD11b nor CD28 after activation, represent the main noncytotoxic functional suppressor cell in the mitogen "activated" suppressor assay. The preferential expansion of CD8+CD28+ cells relative to CD8+CD28- cells, if occurring in vivo in the central nervous system (CNS) compartment, would be consistent with observed phenotypic analysis of cerebrospinal fluid-derived T cells and might contribute to the reduced functional suppressor activity previously found for CNS compared to peripheral blood-derived lymphocytes.

Antibodies, Monoclonal↗

PubMed1992

Differential effects of CD4+ and CD8+ cells in acute, systemic murine candidosis.

Monoclonal antibody (mAb) depletion was used to assess contributions of CD4+ and CD8+ cells in resistance to systemic murine Candida albicans infection. Depletion of CD8+ cells did not influence either survival or mean survival time (MST); however, depletion of CD4+ cells significantly enhanced both survival and MST. Combined depletion of both CD4+ and CD8+ cells significantly lengthened the MST but did not enhance survival. A protective influence of CD8+ cells could be deduced but, to be manifested, required depletion of an overshadowing immunopathologic CD4+ response.

Acute Disease↗

PubMed1991

Quantitative analysis of CD6, CD4 and CD8 cell surface molecules compared to the absolute numbers of CD6+, CD4+ and CD8+ T-cells in peripheral blood in patients with HIV-infection.

T lymphocyte subsets were determined on blood samples from 16 HIV-seropositive patients with manifest AIDS (CDC IV), 24 HIV-seropositive patients with lymphadenopathy syndrome (LAS, CDC III), 16 HIV-seropositive clinical healthy persons (CDC II) and 11 HIV-seronegative homosexuals as control group. Absolute numbers of T-cells (CD6+), T-helper/inducer-cells (CD4+) and T-suppressor/cytotoxic-cells (CD8+), obtained by immunofluorescence staining were compared with the absolute amount of subset specific surface molecules, obtained by a T-cell-ELISA. With both, indirect immunofluorescence technique and ELISA technique a highly significant decrease of the absolute numbers of CD4+ cells and the absolute amount of CD4 surface molecules, respectively, was found in asymptomatic HIV-infection, LAS and in manifest AIDS. In all HIV-seropositive groups the relative decrease of CD4 surface molecules was significantly greater than the decline of CD4+ cells. This phenomenon however was not seen in HIV-seronegative homosexuals. The absolute number of CD6+ cells and the amount of CD6 surface molecules were found significantly lowered in AIDS compared to HIV-seronegative homosexuals. No significant changes were found for CD8+ cell numbers and CD8 surface molecule in the progression of the HIV-infection.

Antigens, CD↗

PubMed1992

Phenotypic expression of integrin membrane receptors on spontaneously proliferating CD8 cells in human T-lymphotropic virus type II (HTLV-II)-infected individuals.

Spontaneous lymphocyte proliferation in the absence of exogenous stimulators was examined in asymptomatic HTLV-II-seropositive (n = 12) and seronegative individuals (n = 16). Mean spontaneous lymphocytic proliferation significantly increased on day 8 postculture in HTLV-II-infected individuals (5762 +/- 899 cpm) compared with normal controls (2034 +/- 925 cpm, P less than 0.01). The proliferating cells in infected individuals were predominantly T cells; neither B cells nor monocytes demonstrated any proliferation. Phenotypic analysis of cultured cells from individuals with HTLV-II infection demonstrated differential expression of integrin molecules as defined by anti-CD29 and anti-S6F1 (42.8 +/- 4.2 and 39.6 +/- 5.9%, respectively) on CD8 cells, as compared with day 0 peripheral blood mononuclear cells (PBMC) from infected individuals (19.7 +/- 3.5 and 19.9 +/- 1.9%, respectively) or normal controls (12.9 +/- 3.1 and 11.5 +/- 2.5%, respectively; P less than 0.001 for both comparisons). These CD8+ cells did not express CD16 or CD11b. The culture supernatants derived from the spontaneously proliferating cells had significantly increased levels of sCD8 and sCD25 (765 +/- 180 and 1805 +/- 320 U/ml, respectively) compared with those from normal controls (222 +/- 120 and 305 +/- 90 U/ml, respectively; P less than 0.01). Furthermore, culture supernatants derived from spontaneously proliferating PBMC from HTLV-II-infected individuals had no detectable levels of HTLV antigen and did not stimulate proliferation of PBMC from normal donors. These results suggest that the spontaneous proliferation in HTLV-II asymptomatic carriers is due to expansion of CD8 cells expressing integrin receptors which may serve as costimulatory molecules for their activation.

Adult↗

PubMed1992

Treatment of fetal thymic organ culture with IL-1 leads to accelerated differentiation of subsets of CD4-CD8- cells.

Using fetal thymic organ culture (FTOC), we describe the effects of IL-1 on T cell differentiation, particularly within the CD4-CD8- subset. While treatment of FTOC with IL-1 led to a modest reduction in total thymocyte yield, it induced an increase in the percentage of CD4-CD8- cells that express IL-2R early in culture and a decrease in the number of their precursors (CD44+IL-2R- cells). The increase in the percentage of cells expressing IL-2R was not accompanied by an increase in the number of these cells. At later time points these IL-2R+ cells (and their precursors) were reduced relative to controls. The total number of CD4-CD8-CD3- precursor cells in IL-1-treated cultures was reduced to approximately half that in controls at Day 12 of culture. However, only minor inhibition of total cell number was observed, which, taken together with the greater frequency of IL-2R+ precursors, suggests that this depletion of the pool of precursors may have been due to the induction of premature differentiation rather than to its inhibition.

Animals↗

PubMed1992

Allograft rejection in CD4+ T cell-reconstituted athymic nude rats--the nonessential role of host-derived CD8+ cells.

PVG-rnu/rnu nude rats reject fully allogenic renal (DA) and skin (BN, AO) allografts after the adoptive transfer of naive CD4+ T cells alone, but rejection is accompanied by the accumulation of many nude-derived CD8+ leukocytes within the graft. In addition, mononuclear cells infiltrating the rejecting renal grafts in these animals display cytotoxic activity in vitro against specific and third-party alloantigens. In this investigation we have treated CD4+ T cell-restored nude rats bearing renal or skin allografts with the mAb MRC OX8 to deplete the host of CD8+ cells. In vivo treatment with OX8 completely eliminated CD8+ cells from rejecting grafts of both kidney and skin, but it did not prevent graft rejection, nor did OX8 treatment abolish the cytotoxic effector cells found in nude rat spleen or in graft-infiltrating cells (GIC) of rejecting renal allografts. The nature of the cytotoxic activity was examined with anti-CD3 mAb 1F4, which was shown to block conventional CD8+ Tc killing in vitro but did not inhibit allogeneic target cell lysis by spleen cells from nude rats. The cytotoxic activity found in GIC of rejecting allografts was not inhibited by anti-CD3 mAb, suggesting that these cytotoxic effector cells were CD3-CD8- and were of extrathymic origin. We conclude that non-thymus-derived CD8+ GIC are not essential for allograft rejection in CD4+ T cell-restored nude rats.

Animals↗

PubMed1992

CD8+ cells and natural cytotoxic activity among spleen, blood, and heart lymphocytes during the acute phase of Trypanosoma cruzi infection in rats.

The infection developed by Wistar Furth rats inoculated with the Y strain of Trypanosoma cruzi was the experimental model used in our study. The results showed that this infection altered considerably the CD4/CD8 lymphocyte subset ratio and the natural cytotoxic activity of mononuclear cells in the spleen, blood, and myocardial tissue. Concomitantly, an expansion of the number of cells expressing major histocompatibility complex (MHC) class II antigens was observed, as well as spontaneous development of high levels of blast cells, mainly in the spleen. The inflammatory infiltration of the myocardium, made up essentially of CD8+ cells (cytotoxic/suppressor T cells, natural killer cells), was initially found at 9 days postinfection, spread continuously, and was observed until the death of the animals at about 18 days postinfection. T. cruzi infection also enhanced the natural killer activity of mononuclear cells in the blood, spleen, and myocardium. Sorting these cells by affinity columns showed that the natural killer function was performed exclusively by the CD8+ population, which did not express MHC class II antigens. It was shown that the polyclonal T-lymphocyte activation induced by T. cruzi infection results in a wide distribution of CD8+ cells with enhanced natural cytotoxic activity in the spleen, blood, and cardiac tissue.

Acute Disease↗

PubMed1992

Frequency of chicken CD4+ and CD8+ cells. Genetic control and effect of Rous sarcoma virus infection.

In chickens from congenic inbred lines CB and CC that differ only in the major histocompatibility complex (MHC), we observed significantly different percentages of CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL) and spleen. Positive cells were detected by indirect immunofluorescence test as analysed by flow cytometry. In both PBL and spleen cell suspensions, the number of CD4+ cells was significantly higher in CB than in CC chickens, whereas in CC birds there was a higher percentage of CD8+ cells than in CB. These statistically significant differences were under the MHC control. We found no statistically significant influence of regressions or progression of Rous sarcoma virus-induced tumours on the percentage of peripheral T cells and on the interleukin-2 production in vitro.

Animals↗

PubMed1992

The viral superantigen Mls-1a induces interferon-gamma secretion by specifically primed CD8+ cells but fails to trigger cytotoxicity.

Superantigens can be operationally defined by their ability to stimulate CD4+ and CD8+ T cells via the T cell receptor beta chain variable domain (TcR V beta). We show here that effector functions of CD8+ T cells specific for superantigens differ depending upon the nature of the superantigen involved. Hence, activated CD8+ T cells bearing TcR V beta specific for the superantigen Mls-1a [encoded in the open reading frame of the 3' long terminal repeat of endogenous mouse mammary tumor virus (MMTV)] are unable to lyse Mls-1a-bearing target cells despite the fact that they release interferon-gamma (IFN-gamma) upon Mls-1a stimulation. In contrast CD8+ T cells specific for the exogenous superantigen staphylococcal enterotoxin B (SEB) readily mediate both lysis and IFN-gamma secretion when exposed to SEB-bearing target cells. This dissociation between lysis and IFN-gamma production by Mls-1a-specific CD8+ T cells is independent of the initial stimulus used for activation and appears not to be simply explained by a low Mls-1a determinant density. We suggest that this phenomenon reflects differing TcR affinity thresholds for lymphokine secretion and cytolysis. Such differences may be exploited by retroviruses such as MMTV in order to escape immunosurveillance.

Animals↗

PubMed1992

Evidence for CD8+ cell increase in long-term PUVA-treated psoriatic patients after PUVA discontinuation.

Long-term PUVA-treated psoriatic patients given maintenance therapy (UVA doses greater than 1,000 J/cm2) have been demonstrated to undergo lymphopenia and a decrease in the total number of circulating CD3+ and CD4+ T cells. The aim of this study was to assess whether the impairment of T cells is detectable also in psoriatic patients after long-lasting PUVA discontinuation. A group of 34 psoriatic patients (25 males, 9 females; mean age 52.7 +/- 12.82 years), who had previously been treated by PUVA therapy (average cumulative dose 1,898.48 +/- 1,207.12 J/cm2), was studied 1 year or more after discontinuation of PUVA therapy. The patients studied failed to show any impairment in CD3+ and CD4+ cells. Nevertheless, a significant increase (p less than 0.05) in circulating CD8+ cells (both in the percentage and the total number) was detectable in PUVA patients as compared to appropriate controls. The significance and implications of this finding are not known and need further investigations.

CD4-CD8 Ratio↗

PubMed1992

Mechanism of protection from graft-versus-host disease mortality by IL-2. III. Early reductions in donor T cell subsets and expansion of a CD3+CD4-CD8- cell population.

Reducing the graft-vs-host disease (GVHD)-promoting capacity of allogeneic T cells while maintaining alloengraftment and graft-vs-leukemia effects remains an important but elusive goal in clinical bone marrow transplantation (BMT). We have recently demonstrated that a short course of high dose IL-2 administered at the time of BMT has a powerful protective effect against GVHD mortality in mice. This short course of IL-2 is able to protect mice from both acute and chronic GVHD without sacrificing alloengraftment or graft-vs-leukemia effects of allogeneic T cells. Because the early administration of IL-2 seems to be crucial for this effect, we have studied the early lymphoid repopulation events after lethal irradiation and allogeneic BMT. These studies show that there are consistent delays in splenic repopulation by allogeneic cells after BMT in IL-2-treated animals compared with their untreated cohorts. Even greater percent reductions were seen in donor splenic T cell populations in the first few days after BMT in IL-2-treated animals. Splenic cells with the CD3+CD4-CD8- phenotype were increased in IL-2 treated animals at days 3 and 4 after BMT. This phenotype resembles that of bone marrow-derived cells which have been previously shown to inhibit GVHD, suggesting a possible mechanism for the protective effect of IL-2.

Animals↗

PubMed1992

A factor from CD8 cells of human immunodeficiency virus-infected patients suppresses HLA self-restricted T helper cell responses.

Defective in vitro T helper cell (Th) function can occur in asymptomatic human immunodeficiency virus (HIV)-seropositive (HIV+) individuals. A characteristic, early finding is the loss of an in vitro response to recall antigens, such as influenza A virus (FLU), despite an intact Th response to alloantigen (ALLO). To determine whether suppressor cells and/or inhibitory factors could contribute to this HIV-associated Th immunodeficiency, coculture studies were performed using peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV-infected (HIV+) and one of whom was uninfected (HIV-seronegative, HIV-). In vitro Th function was measured as interleukin 2 production or proliferation to FLU and ALLO. Two pairs of twins were repetitively studied. A single HIV+ individual with multiple samples of cryopreserved PBLs over 6 years (including a HIV- specimen) was also studied. PBLs from the HIV+, but not from the HIV-, individuals demonstrated defective in vitro Th function in response to FLU but not to ALLO. PBLs from HIV+ individuals could induce a similar defect in the Th function of syngeneic or autologous HIV- PBLs. This suppression was generated by CD4-depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8+ cells of HIV+ donors was generated by 24-hr unstimulated cultures of HIV+ PBLs. This factor inhibited FLU but not ALLO responses of autologous, syngeneic, or allogeneic HIV- PBLs. This suppressive effect could not be explained by HIV infection or replication during the culture period. These results demonstrate that selective abrogation of Th function to recall antigens in HIV+ individuals is associated with an inhibitory factor produced by CD8+ T cells.

CD8 Antigens↗

PubMed1992

Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells.

Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.

Animals↗