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Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer. Summary of "Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer." Regulatory T (Treg) cells are a subpopulation of T cells with the ability to control the responses of both CD4+ and CD8+ T cells. A case-control study was conducted in order to determine the functional attributes of Treg cells within the breast cancer milieu. Triple-color flow cytometry was utilized to study the phenotype expression of CD4+CD25+ Treg cells and CD8+ T cells in autologous tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) derived from 33 patients with stage I-III breast cancer. The prevalence of CD4+CD25+ T cells was significantly higher in TILs than in PBLs. The expressions of FOXP3 and GITR in CD4+CD25+ Treg cells were lower in PBLs than in TILs. Functional studies showed that both granzyme B and perforin were barely expressed in peripheral Treg cells but were highly expressed in Treg cells in the tumor microenvironment. On the contrary, down-regulation of both granzyme B and perforin expressed in the CD8+ cytotoxic T lymphocytes was significantly lower in TILs than in PBLs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules were synchronously up-regulated in CD8+ cytotoxic T cells. The in vitro kinetic study showed that adequate activation of TILs derived from breast cancer tissue could restore the appropriate antitumor immune response. Affiliation Department of Surgery, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan. Journal Details This article was published in the following journal. Name: Immunologic research Pages: Links - PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21918886 PubMed Articles Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to spe... Interleukin-1 receptors are differentially expressed in normal and psoriatic T cells. This study was carried out to examine the possible role of interleukin-1 (IL-1) in the functional insufficiency of regulatory T cells in psoriasis, by comparing the expression of IL-1 receptors on hea... Regulation of MHC Class I Expression by Foxp3 and Its Effect on Regulatory T Cell Function. Expression of MHC class I molecules, which provide immune surveillance against intracellular pathogens, is higher on lymphoid cells than on any other cell types. In T cells, this is a result of activa... Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics. There is no nationally or internationally binding definition of the term "cytotoxic drug" although this term is used in a variety of regulations for pharmaceutical development and manufacturing of dru... Regulation of mIkBNS stability through PEST-mediated degradation by proteasome. Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be ... Clinical Trials Rapamycin and Regulatory T Cells in Kidney Transplantation The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell w... Importance of CD4+CD25+ly in UC1. Investigation of Difference Between Blood Concentration IL 17, IL 33, Regulatory T ly in Patients With UC and Control Group Mucosal inflammation in patients with UC is the result of immunosuppression disturbance because decreasing number of regulatory T ly and activation IL 17 Lymphoid follicles, consisting of T-and B cells, are involved in the chronic inflammatory response in COPD. Foxp3 positive regulatory T cells (Tregs) are present in these follicles and may... Adolescence, Puberty, and Emotion Regulation The purpose of this study is to use brain imaging technology to compare how the brains of adolescents and adults are activated during tasks that involve emotional responses. Evidence sugg... Role of Regulatory T Cells in Pathogenesis of Primary IgA Nephropathy Along structural IgA abnormalities, hyperproduction of IgA is thought to play a role in the pathogenesis of primary IgA nephropathy. CD4+CD25+Fox3P regulatory T cells are instrumental in s... Medical and Biotech [MESH] Definitions Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Cathepsin W A cysteine endopeptidase found in NATURAL KILLER CELLS and CYTOTOXIC T-LYMPHOCYTES. It may have a specific function in the mechanism or regulation of cytolytic activity of immune cells. Down-regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Up-regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Cd8-positive T-lymphocytes A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
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Boras, Zagorka (2004) Citokinski profil limfocita T iz krvi i bronhoalveolarnog ispirka u bolesnika s plućnom tuberkulozom [ Cytokine profile of T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid in patients with active pulmonary tuberculosis ]. PhD thesis, Sveučilište u Zagrebu. Abstract Cell-mediated immunity, especially from CD4+ T-lymphocyte function, plays an important role in eliminatig mycobacteria in tuberculosis. Reports on Th1-type and Th2-type cytokines in human tuberculosis are conflicting, and little is known about their role in tissue damage. We examined the cytokine responses of CD4+ and CD8+ T-lymphocytes in peripheral blood and bronchoalveolar lavage fluid (BAL) from 20 purified protein derivative skin-positive (PPD+) and from nine PPD skin-negative patients with active pulmonary tuberculosis. Parallel blood and BAL fluid samples from each subject were shortly incubated with or without PMA and ionomycin, and the proportions of CD4+ and CD8+ T-lymphocytes producing interferon- (IFN-) or interleukin-4 (IL-4) were measured by flow cytometry. There was no age or BMI difference of examiness between PPD+ and PPD- group. PPD- patients, in relation to PPD+ patients, had a significant higher percent of CD4+ T-lymphocytes in the BAL. No significant difference was found between groups in percent CD4+ T-lymphocytes in peripheral blood and CD8+ T-lyphocytes peripheral blood and BAL. At the same time, PPD- patients have shown a significant higher percent of CD4+ T-lymphocytes which produced IFN- in relation to the entire number activated CD4+ T-lymphocytes in a peripheral blood. No significant difference was found in the production IFN- of CD8+ T-lymphocytes peripheral blood and BAL and CD4+ T-lymphocytes in the BAL. CD4+ T-lymphocytes of peripheral blood in two PPD-patients produced IL-4 while the rest of the T-lymphocytes peripheral blood and BAL suppressed the production of this cytokine. Among PPD+ patients group we have found a higher percent of CD4+ as well as CD8+ T-lymphocytes which produce IFN- in BAL in relation to the peripheral blood, while the BAL in PPD- group was more active only in CD4+ production IFN-. These results suggest a higher immune activity in the blood of PPD- patients while the BAL is more active in both groups of examinees in relation to the peripheral blood. It suggests that the separation of T-lymphocytes, specially those producing IFN- from peripheral blood to the lungs, occurs in tuberculosis. Abstract in Croatian Stanicama je posredovana imunost, naročito CD4+ T-limfocitima, ključna u eliminaciji mikobakterija u tuberkulozi. Dosadašnja saznanja o Th1 i Th2 tipu citokinske proizvodnje u ljudskoj tuberkulozi konfliktna su i malo se zna o njihovoj ulozi u tkivnom oštećenju. Mi smo istraživali citokinski odgovor CD4+ i CD8+ T-limfocita periferne krvi i BAL-a u 20 PPD+ i devet PPD- bolesnika s aktivnom plućnom tuberkulozom. Uzorci periferne krvi i BAL-a svakog bolesnika bili su kratkotrajno inkubirani s PMA i ionomicinom ili bez njih, nakon čega smo na protočnom citometru određivali CD4+ i CD8+ T-limfocite koji su proizvodili IFN- ili IL-4. Između PPD+ i PPD- skupine nije bilo razlike u dobi ispitanika i BMI. PPD- bolesnici su, u odnosu na PPD +, imali značajno veći postotak CD4+ T-limfocita u BAL-u. Nije bilo značajnije razlike među grupama u postotku CD4 T-limfocita u perifernoj krvi i CD8+ u perifernoj krvi i BAL-u. Istovremeno, PPD- bolesnici iskazali su značajno veći postotak CD4+ T-limfocita u perifernoj krvi koji su proizvodili IFN-, a u odnosu na sveukupni broj tih aktiviranih CD4+ T-limfocita. Nije bilo razlike između skupina u proizvodnji IFN- od CD8+ T-limfocita krvi i BAL-a i CD4+ T-limfocita BAL-a. CD4+ T-limfociti periferne krvi dva PPD- bolesnika su proizvodili IL-4, a ostali su T-limfociti periferne krvi i BAL-a zakazali u proizvodnji navedenog citokina. Unutar PPD+ skupine bolesnika našli smo značajno veći postotak i CD4+ i CD8+ T-limfocita koji proizvode IFN- u BAL-u u odnosu na perifernu krv, dok je u PPD- skupine BAL bio aktivniji samo u CD4+ proizvodnji IFN-. Ovakvi rezultati sugeriraju veću imunološku aktivnost u PPD- bolesnika u krvi, a BAL je obje skupine ispitanika aktivniji u odnosu na perifernu krv. Sve to sugerira da u tuberkulozi dolazi do odjeljivanja T-limfocita, naročito onih koji proizvode IFN-, iz periferne krvi u pluća. Actions (login required) Downloads Downloads per month over past year