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CD8+ T Lymphocytes (cd8+ t + lymphocyte)
Selected AbstractsAllergic contact dermatitis: the cellular effectorsCONTACT DERMATITIS, Issue 1 2002Ian Kimber Contact hypersensitivity reactions are mediated by lymphocytic effector cells. Until recently it was believed that the most important of these were CD4+ T lymphocytes. However, there is growing evidence that in many instances the predominant effector cell may be a CD8+ T lymphocyte, with in some instances CD4+ cells performing a counter-regulatory function. Here we review the roles of CD4+ T helper (Th) cells and CD8+ T cytotoxic (Tc) cells, and their main functional subpopulations (respectively, Th1 and Th2 cells and Tc1 and Tc2 cells) in the elicitation of contact hypersensitivity reactions and consider the implications of effector cell selectivity for the biology of allergic contact dermatitis. [source] Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus,CYTOMETRY, Issue 4 2009Susana Mellor-Pita Abstract Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNF,), interferon gamma (IFN,), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNF, levels were increased in patients (P , 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P , 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNF,+ (P= 0.02), CD4+IFN,+ (P = 0.04) and CD8+ IFN,+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society [source] Processing and presentation of (pro)-insulin in the MHC class II pathway: the generation of antigen-based immunomodulators in the context of type 1 diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2010Timo Burster Abstract Both CD4+ and CD8+ T lymphocytes play a crucial role in the autoimmune process leading to T1D. Dendritic cells take up foreign antigens and autoantigens; within their endocytic compartments, proteases degrade exogenous antigens for subsequent presentation to CD4+ T cells via MHC class II molecules. A detailed understanding of autoantigen processing and the identification of autoantigenic T cell epitopes are crucial for the development of antigen-based specific immunomodulators. APL are peptide analogues of auto-immunodominant T cell epitopes that bind to MHC class II molecules and can mediate T cell activation. However, APL can be rapidly degraded by proteases occurring in the extracellular space and inside cells, substantially weakening their efficiency. By contrast, protease-resistant APL function as specific immunomodulators and can be used at low doses to examine the functional plasticity of T cells and to potentially interfere with autoimmune responses. Here, we review the latest achievements in (pro)-insulin processing in the MHC class II pathway and the generation of APL to mitigate autoreactive T cells and to activate Treg cells. Copyright © 2010 John Wiley & Sons, Ltd. [source] CD4+ T cell help improves CD8+ T cell memory by retained CD27 expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Matthias Abstract CD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27high whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27,/, memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory. [source] Characteristic appearances of the bone marrow in T-cell large granular lymphocyte leukaemiaHISTOPATHOLOGY, Issue 5 2007N Osuji Aims:, To augment the limited literature on bone marrow (BM) appearances in T-cell large granular lymphocyte (LGL) leukaemia and to identify a histological signature to aid in diagnosis of this condition. Methods and results:, A descriptive analysis of the histology of the BM in T-cell LGL leukaemia was performed (n = 38). Antibodies against CD3, CD4, CD5, CD8, CD16, CD56, CD57 and CD20 or CD79a were employed. Antibodies against CD68 (macrophages) and CD34 (sinusoids) were also included. BM was normocellular or hypercellular in the majority of cases, with interstitial lymphoid infiltration in 97%. Lymphoid nodules were present in 55% and intrasinusoidal permeation in 58%. Apoptotic figures and haemosiderin deposition were common. All cases showed trilinear haematopoiesis with normal or increased megakaryopoiesis and erythropoiesis, but normal/reduced myelopoiesis. Reticulin was increased (Grade II,III). Immunohistochemistry revealed interstitial infiltration in all cases and helped to identify lymphoid nodules in two-thirds of cases. Preferential localization of CD8+ T lymphocytes to the interstitium and CD4+ T lymphocytes to the periphery of CD20+ B-cell nodules was seen in almost 90% of cases. Conclusions:, Nodules with non-clonal B-cell centres surrounded by CD4+ cells, with interstitial CD8+ cells, are a characteristic finding in T-cell LGL leukaemia and may represent a histological signature for this condition. [source] Expression of CD8, identifies a distinct subset of effector memory CD4+ T lymphocytesIMMUNOLOGY, Issue 2 2006Iole Macchia Summary Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8,, homodimer, while the minor population was CD4lo CD8hi and expressed the CD8,, heterodimer. The majority of CD4hi CD8,lo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7, CD28, HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8,lo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8,lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8,lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8, represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection. [source] Two Japanese cases of lichen planus pigmentosus-inversusINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2007Aki Kashima MD Case 1 was a 51-year-old Japanese woman. She presented with an asymptomatic brown macule located on the right axilla of 2 months' duration. The smooth macule was 2 cm in diameter with a sharp demarcation (Fig. 1A). Figure 1. Photographs of skin lesions in two patients. (A) Case 1. Well-circumscribed brown macule without an active red border in the central portion of the right axilla. (B) Case 2. Symmetric distribution of brown macules without an active red border in the popliteal fossae Case 2 was a 62-year-old Japanese man. He presented with asymptomatic, symmetric, gray,brown macules located on the groin, axillae, and popliteal region of 6 months' duration. The smooth macules were several millimeters to centimeters in diameter and sharply demarcated (Fig. 1B). Oral or nail lesions, previous inflammatory processes in affected areas, and internal malignancies were absent. A causal relationship with drugs, recent sun exposure, or trauma could not be identified. Findings for work-up, including blood cell count, fasting blood sugar levels, liver function, serum electrolyte levels, serum electrophoresis, urinalysis, antinuclear antibodies, and serological examinations for human hepatitis viruses and syphilis, were within normal limits or negative. The lesions gradually disappeared without medication within 6 months. Biopsy specimens showed a lymphocytic infiltrate with basal vacuolar changes and prominent melanin incontinence in the upper dermis (Fig. 2A). The band-like lymphocytic infiltrate was moderate in Case 1 and mild in Case 2. Immunohistochemistry showed infiltrative CD8+ T lymphocytes with keratinocytic damage, indicating cytotoxic injury of the keratinocytes (Fig. 2B). Both the epidermis and the upper dermis contained CD1a+ cells (Fig. 2C). The keratinocytes focally and weakly expressed HLA-DR (Fig. 2D). These findings were identical in samples from both patients. Figure 2. Light and immunohistochemical microphotographs. (A) Mild, band-like, lymphocytic infiltrate with basal vacuolar change and prominent melanin incontinence in the upper dermis with apoptosis or necrosis of keratinocytes. (B) Epidermal infiltrate of CD8+ T lymphocytes with keratinocytic damage. (C) CD1a+ cells in the upper dermis. (D) Keratinocytes focally and weakly express HLA-DR (original magnifications: A, ×200; B,D, ×400) [source] Evidence for a perforin-mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infectionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2002ANDREA HENRIQUES-PONS Summary. ,CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (,/,) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (,/,) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (,/,) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (,/,) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (,/,) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi. [source] Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infectionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2006D. McIlroy Summary Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral replication during human immunodeficiency virus (HIV) infection. However, the efficacy of the CTL response varies between individuals. We tested the hypothesis that genetic polymorphisms in the lytic effector molecule perforin could influence the progression of HIV infection. The perforin gene was screened for single nucleotide polymorphisms (SNPs) by denaturing high-performance liquid chromatography (dHPLC). Correlations were sought between perforin genotype, perforin expression and lytic function of CD8+ T lymphocytes from HIV-positive patients. Association of perforin genotype with disease progression was investigated in 426 seroconverters enrolled in the French SEROCO cohort. AIDS-free survival curves were constructed using the Kaplan,Meier method and compared using the log-rank test. Three SNPs were found in the proximal promoter region of the perforin gene: 63G (allelic frequency 0.029), 112G (allelic frequency 0.071) and 1012T (allelic frequency 0.070). The presence of the 1012T genotype correlated with fewer perforin+ cells among circulating CD8+ CTL. However, CTL lines from HIV -positive individuals heterozygous for the perforin 1012T SNP displayed normal lysis of target cells, and within the SEROCO cohort, patients heterozygous for the 1012T SNP showed normal disease progression. However, 1012T/T homozygotes showed a tendency towards slower disease progression (P = 0.08). In conclusion, polymorphism in the perforin gene is limited, and although the 1012T genotype appears to influence perforin expression, it was not conclusively associated with disease progression in HIV infection. [source] Correlation between radiculalgia and counts of T lymphocyte subsets in the peripheral blood of patients with lumbar disc herniationORTHOPAEDIC SURGERY, Issue 4 2009Peng Tian MD Objective:, To determine the correlation between the degree of radiculalgia and counts of T lymphocyte subsets in the peripheral blood of patients with lumbar disc herniation. Methods:, Forty-nine patients with lumbar disc herniation (group A) were divided into three subgroups according to Visual Analogue Scale (VAS) pain scores (group A1: n= 12, VAS 0,4.0; A2: n= 24, VAS 4.1,7.0; A3: n= 13, VAS 7.1,10.0. Twenty health blood donors who volunteered to be involved in the study comprised the control group (group B). Peripheral blood counts of various T lymphocyte subsets were measured in each group. Results:, (i) The counts of CD4+ T and CD4+/CD8+ lymphocytes were higher in group A than in group B, and the difference between the two groups was statistically significant (P < 0.05). There were also statistically significant differences between group A and group B in the counts of CD3+ and CD8+ T lymphocytes (P < 0.05); (ii) There was no correlation between the VAS scores and the counts of CD3+ T lymphocytes (r= 0.194, P > 0.05). A strong significant correlation was observed between the VAS scores and counts of CD4+ T lymphocytes (r= 0.542, P < 0.05), CD4+/CD8+ (r= 0.468, P < 0.05), which increased with increasing VAS scores in the three subgroups of group A (P < 0.05). However there was a significant negative linear correlation between CD8+ T lymphocyte counts and pain scores (r=,0.462, P < 0.05). Conclusion:, Our results suggest that changes in T lymphocyte subsets in peripheral blood take place after prolapse of lumbar intervertebral discs. The current results may provide support for involvement of immunologic mechanisms in low back pain secondary to herniation of the lumbar disc. T lymphocytes may play an important role in the development of symptoms in patients with lumbar intervertebral disc herniation. [source] Proteomic and transcriptomic analysis of human CD8+ T lymphocytes over-expressing telomerasePROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2007Lynne Thadikkaran Abstract Human T lymphocytes have a finite life span resulting from progressive telomere shortening that occurs at each cell division, eventually leading to chromosomal instability. It has been shown that ectopic expression of the human telomerase reverse transcriptase (hTERT) gene into various human cells results in the extension of their replicative life span, without inducing changes associated with transformation. However, it is still unclear whether cells that over-express telomerase are physiologically and biochemically indistinguishable from normal cells. To address this question, we compared the proteome of young and aged human CD8+ T lymphocytes with that of T cells transduced with hTERT. Interestingly, we found no global changes in the protein pattern in young T cells, irrespective of telomerase expression. In contrast, several relevant proteins with differential expression patterns were observed in hTERT-transduced T cells with extended life span upon long-term culture. Altogether, our data revealed that T lymphocytes over-expressing telomerase displayed an intermediate protein pattern, sharing a similar protein expression not only with young T cells, but also with aged T cells. Finally, the results obtained from this global proteomic approach are in agreement with the overall gene transcription profiling performed on the same T-cell derived clones. [source] Islet Allograft Rejection by Contact-Dependent CD8+ T cells: Perforin and FasL Play Alternate but Obligatory Roles,AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2007M. Sleater Though CD8+ T lymphocytes are important cellular mediators of islet allograft rejection, their molecular mechanism of rejection remains unidentified. Surprisingly, while it is generally assumed that CD8+ T cells require classic cytotoxic mechanisms to kill grafts in vivo, neither perforin nor FasL (CD95L) are required for acute islet allograft rejection. Thus, it is unclear whether such contact-dependent cytotoxic pathways play an essential role in islet rejection. Moreover, both perforin and CD95L have been implicated in playing roles in peripheral tolerance, further obscuring the role of these effector pathways in rejection. Therefore, we determined whether perforin and/or FasL (CD95L) were required by donor MHC-restricted (,direct') CD8+ T cells to reject islet allografts in vivo. Islet allograft rejection by primed, alloreactive CD8+ T cells was examined independently of other lymphocyte subpopulations via adoptive transfer studies. Individual disruption of T-cell-derived perforin or allograft Fas expression had limited impact on graft rejection. However, simultaneous disruption of both pathways prevented allograft rejection in most recipients despite the chronic persistence of transferred T cells at the graft site. Thus, while there are clearly multiple cellular pathways of allograft rejection, perforin and FasL comprise alternate and necessary routes of acute CD8+ T-cell-mediated islet allograft rejection. [source] Immunological effects of stress in psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2009G. Schmid-Ott Summary Background, Psychological stress causes phenotypic changes in circulating lymphocytes and is regarded as an important trigger of the Th1-polarized inflammatory skin disease psoriasis. Objective, To study the effects of psychological stress on immunological parameters, i.e. membrane molecules relevant to the pathophysiology of psoriasis, especially cutaneous lymphocyte-associated antigens (CLA) involved in T and natural killer (NK) cells homing in on the skin. Methods, The severity of psoriasis was assessed in patients using the Psoriasis Area and Severity Index. Patients with psoriasis (n = 15) and healthy volunteers (n = 15) were exposed to brief psychological stress in the laboratory. In vitro analyses were conducted 1 h before, immediately following and 1 h after stress exposure. Peripheral T- and NK-cell subsets including CD8+ T lymphocytes, CLA+ lymphocytes and lymphocyte function-associated antigen type 1 (LFA-1)+ lymphocytes were analysed by flow cytometry. Results, We found a significant stress-induced increase of CD3+ T lymphocytes in patients with psoriasis only. Analyses of T-cell subsets revealed that this increase was observable for cytotoxic CD8+ T lymphocytes and CLA+ CD3+ lymphocytes. The total number of circulating NK cells (CD16+, CD56+) increased immediately after stress in both groups whereas only patients with psoriasis showed a significant increase in CLA+ NK cells. Conclusions, A higher stress-induced increase of CLA+ T and CLA+ NK cells in the circulation of patients with psoriasis might point to an increased ability of T and NK cells in the presence of psoriasis to home in on the skin during mental stress. Further studies are needed to verify these relationships in more detail and to investigate the time point at which these cells accumulate within lesional skin, and whether or not psychotherapy improves the quality of life of patients with psoriasis and influences stress-dependent parameters. [source] Human red blood cells have an enhancing effect on the relative expansion of CD8+ T lymphocytes in vitroCELL PROLIFERATION, Issue 6 2001B. Porto The present study was designed to analyse the effect of red blood cells on T-cell proliferation and expansion. A comparative study was done in peripheral blood cell cultures stimulated with phytohemagglutinin, with or without red blood cells. The presence of red blood cells had a consistent enhancing effect on T lymphocyte proliferation, as determined by an increase in both the mitotic index and thymidine uptake. Phenotypic characterization of T cell blasts by flow cytometry revealed that, in the presence of red blood cells, expanding cells were preferentially CD8+ cells. Accordingly, proliferation of CD8+ lymphocytes from two patients with CD8+ hyperlymphocytosis was dependent on the presence of red blood cells. In contrast, proliferation of CD4+ lymphocytes from two patients with CD4+ hyperlymphocytosis was strongly inhibited by the presence of red blood cells. This is the first reported evidence that human red blood cells have an enhancing effect on the expansion of CD8+ lymphocytes in vitro. [source] Wasp venom immunotherapy induces a shift from IL-4-producing towards interferon-gamma-producing CD4+ and CD8+ T lymphocytesCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2001A. J. Schuerwegh Background Venom immunotherapy (VIT) has proven to be very effective in hymenoptera venom anaphylaxis. However, the underlying immunoregulatory mechanisms of venom immunotherapy remain poorly understood. Recent studies measured the total amount of cytokine in culture supernatans, suggesting a shift in cytokine production from Th2 to a Th1 cytokine profile during VIT. We wanted to examine the contribution of specific T lymphocyte subpopulations, which is impossible using an extracellular method to determine cytokines in supernatants. Objective The present study was designed to evaluate the effect of VIT on the percentages of type 1 (IL-2, interferon-gamma (IFN-,)) and type 2 (IL-4) CD4+ and CD8+ T lymphocytes of patients with wasp venom anaphylaxis during immunotherapy. Methods Peripheral blood mononuclear cells of 20 individuals with a history of wasp sting anaphylaxis and a positive serum wasp venom specific IgE were isolated and in vitro stimulated with phorbol-12-myristate-13-acetate and ionomycin before VIT, at the end of a 5-day semirush VIT and at 6 months during VIT. Three-colour flow cytometric analysis was used for intracellular cytokine (IL-2, IFN-,, IL-4) detection in CD4+ (CD3+CD8,) T lymphocytes and CD8+ (CD3+CD8+) T lymphocytes. Results At the end of a 5-day semirush VIT, there was a significant decrease in percentage of IL-4-producing CD4+ and CD8+ T cells, compared with cytokine-producing cells before VIT (P = 0.0002 and 0.004). After 6 months of VIT, patients showed an increased number of IL-2-producing stimulated CD4+ and CD8+ lymphocytes compared with values before VIT (P = 0.002 and P = 0.0003). A higher amount of IFN-,-producing stimulated CD4+ and CD8+ cells was found after 6 months of VIT (P = 0.001 and P = 0.0006). There was no correlation between cytokine-producing cells and specific IgE for wasp. Conclusion Venom immunotherapy induced a shift from IL-4-producing towards IFN-,-producing CD4+ as well as CD8+ T lymphocytes. [source] | ||||||||||||||||||||||||||||