Cellular immunity is an important component of human immune system and plays a crucial role in the fight against tumor cell or invasive pathogens. Researches on cell-based immunotherapy have long been focused on eliciting tumor-specific CD8+ cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. However, the resulting treatments have been surprisingly poor at inducing complete tumor rejection, in both the experimental models and clinical trials. The CD4+ T cells has been studied mainly for their role as helpers for CD8+ CTL, even suggesting that the tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. Recent studies indicated that CD4+T cells are not a pure cell lineage with single function, but a cell population with complex functions. Moreover CD4+ T cells may not only be helper cells, but also act as potent effector cells or partners with NK cells that can clear a wide variety of tumors. In a word, the antitumor potential of effector CD4+ T cells might have been underestimated. In this article, the classification and differentiation of CD4+ T cells, the function and secreted cytokines of CD4+ T cells, the CD4+ T cells and tumor immune, the tumor-immuno regulatory effects of CD4+ T cells, and clinical researches of CD4+ T cells are reviewed.
CD4-Positive T-Lymphocytes ; classification ; cytology ; immunology ; Cytokines ; metabolism ; Cytotoxicity, Immunologic ; Humans ; Immunity, Cellular

OBJECTIVESTo compare the in vitro killing effects of cytotoxic T lymphocytes (CTLs) induced by dendritic cells(DCs) that modified with 4 different specific hAFP-derived peptides.

METHODSDCs derived from normal human peripheral monocytes were activated by GM-CSF and IL-4. MTT assay was applied to analyse the proliferation activities of the DCs. To induce the specific CTLs, DCs modified with four immunodominant epitopes from alpha fetoprotein (AFP) were cocultured with MNC derived CD8+ lymphocytes. The acquired specific CTLs were cocultured with SMMC-7721 cells at different dilutions, and the killing effects were detected by flow-cytometry and Non-Radioactive Cytotoxity kit.

RESULTSThe CTLs stimulated by DCs modified with the four immunodominant epitopes from alpha fetoprotein (AFP) had specific killing activities on the SMMC-7721 cells. And statistical differences of the killing effects existed between the hAFP(158-166) (FMNKFIYEI) group and the other three groups.

CONCLUSIONCTLs induced by the DCs modified with the four immunodominant peptides had significant killing effects on the hepatocellular cancer cells in vitro. The hAFP(158-166) (FMNKFIYEI) peptide had a relatively higher efficiency in inducing DCs and stimulating specific CTLs.

Cell Line, Tumor ; Cell Proliferation ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Humans ; Peptides ; immunology ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; alpha-Fetoproteins ; classification ; immunology

Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.
Aging/*immunology ; Animals ; Cytokines/genetics/metabolism ; Female ; Gene Expression Regulation ; Malaria/*immunology/*parasitology ; Mice ; Plasmodium berghei/*classification ; T-Lymphocytes, Regulatory/classification/*physiology

Several parameters of cell-mediated immunity thirty-eight patients with end stage chronic renal failure were measured including total lymphyocytes, B-and T-lymphocytes, T-cell subsets and the mitogenic reponse to PHA and Con A at three different times; before dialysis, 3 months and 12 months after dialysis treatment. There were no significant differences in the absolute numbers of peripheral leukocytes between each patient and the control group. But the absolute numbers of lymphocytes of each patient group were significantly reduced compared to the control group (p< 0.01). The proportion of peripheral blood active T cells and helper T cells was significantly reduced both in the predialysis uremic and dialysis populations compared to the control group, although the helper/suppressor(OKT4/OKT8) ratio was not different between each patient and the control group except for a lower ratio in the hemodialysis 12 month follow-up group (HD 12M). With respect m the PHA and Con A stimulation tests, the stimulation indices of the predialysis and hemodialysis groups were significantly lower than those of the control group. However, patients on continuous ambulatory peritoneal dialysis (CAPD) exhibited a normal mitogenic response and a lower suppressor cell removal index compared to the patients on hemodialysis, suggesting an improved cell-mediated immunity in the patients undergoing CAPD.
Adult ; Aged ; B-Lymphocytes/*immunology ; Comparative Study ; Human ; In Vitro ; Kidney Failure, Chronic/*immunology/therapy ; Lectins/pharmacology ; Leukocyte Count ; Lymphocyte Activation/drug effects ; Middle Age ; Peritoneal Dialysis, Continuous Ambulatory ; Renal Dialysis ; Support, Non-U.S. Gov't ; T-Lymphocytes/classification/*immunology ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Suppressor-Effector/immunology

Th17(T helper 17 cell), a newly discovered subset of T cells is associated with IL-23 and characterized by production of IL-17, the functions of which are distinct from those of Th1, Th2 and Treg subsets. The development of Th17 cells can be promoted by TGF-beta1, IL-6, and IL-23; but inhibited by IFN-gamma, IL-4 and Socs3. It is clear that Th17 cells have protective effects on body by facilitating the pro-inflammatory responses. On the other hand, the role of Th17 cells in the pathophysiology of autoimmune diseases has been described.
Autoimmune Diseases ; immunology ; physiopathology ; Interleukin-17 ; biosynthesis ; immunology ; Interleukin-23 ; biosynthesis ; genetics ; T-Lymphocyte Subsets ; immunology ; physiology ; T-Lymphocytes, Helper-Inducer ; classification ; cytology ; immunology ; Transforming Growth Factor beta1 ; biosynthesis ; genetics

The studies have provided the first comprehensive comparison of the factors regulating activation and proliferation of WC1+ and WC1- gammadelta T cells. The investigation has shown that accessory molecules essential for activation and function of WC1+ and WC1- gammadelta T cells and the sources and roles of cytokines in activation of gammadelta T cells through the T cell receptor (TCR). The study has also shown that the role of cytokines in activation and function of gammadelta T cells activated indirectly through cytokines secreted by ab T cells, accessory cells and antigen presenting cells (APC). Cytokines were differentially produced by subpopulations of gammadelta T cells under different conditions of activation. The investigation obtained in this study has revealed that factors account for activation and proliferation of gammadelta T cells in cultures designed to study MHC-restricted responses to antigens. Evidence obtained here has shown there is biological relevance to activation under these culture conditions that points to potential regulatory and effector functions of gammadelta T cells. The investigations have also provided the information needed to begin identifying and characterizing antigens recognized by the TCR repertoires of WC1+ and WC1- gammadelta T cells. Finally, the investigations have provided the information needed to begin analysis of the mechanisms by which gammadelta T cells modulate MHC restricted immune responses to pathogens and derived vaccines.
Animals ; Base Sequence ; Cattle ; Concanavalin A ; Cytokines/genetics/immunology ; DNA Primers ; Immunophenotyping ; Lymph Nodes/immunology ; Lymphocyte Activation ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/classification/*immunology

OBJECTIVETo determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China.

METHODSHIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks.

RESULTSFor M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P < 0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P > 0.05).

CONCLUSIONCD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.

Adult ; CD4-Positive T-Lymphocytes ; immunology ; virology ; China ; Female ; HIV ; classification ; isolation & purification ; pathogenicity ; HIV Infections ; virology ; HIV Seronegativity ; immunology ; Humans ; In Vitro Techniques ; Male ; Sexual Partners

OBJECTIVETo explore the relationship between CD8+ T-cell CD28 molecular expression in peripheral blood and TCM type in patients with chronic aplastic anemia (CAA).

METHODSUsing flow cytometry to detect the CD28 expression in 45 in-patients or out-patients and 24 healthy subjects for control. And the relation with TCM type was analyzed from the immunological aspect.

RESULTS(1) The levels of CD8, CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients than those in the healthy subjects (P < 0.05 or P < 0.01). (2) The levels of CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients of Shen-Yin deficiency type than those in the CAA patients of Shen-Yang deficiency type (P < 0.05 or P < 0.01).

CONCLUSION(1) The abnormal high expression of peripheral blood co-stimulatory molecules CD28 suggested CD28 disorder may play an important role in immuno-pathogenesis of CAA. (2) The levels of peripheral CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- can be taken as an objective indexes for TCM typing of CAA, which was disordered more severe in patients of Shen-Yin deficiency type than in those of Shen-Yang deficiency type.

Adult ; Anemia, Aplastic ; classification ; diagnosis ; immunology ; CD28 Antigens ; biosynthesis ; CD8-Positive T-Lymphocytes ; immunology ; Chronic Disease ; Diagnosis, Differential ; Humans ; Kidney Diseases ; immunology ; Male ; Medicine, Chinese Traditional ; Yang Deficiency ; immunology ; Yin Deficiency ; immunology

OBJECTIVETo characterize the Gag-Specific T lymphocyte responses and identify immunodominant region recognized in Chinese HIV-1 recombinant subtype B/C infectors.

METHODS10 antiretroviral treatment (ART) naive HIV-1 recombinant subtype B/C infectors with infected time in 1 year, 25 ART-naive infectors with infected time > 3 years and 10 HIV-1-seronegative healthy individuals were enrolled. HIV-1-specific T lymphocyte responses were analyzed by an IFN-gamma Elispot assay against 123 overlapping peptides spanning HIV-1 Gag protein in the present study.

RESULTSGag-specific T lymphocyte responses of interferon-gamma secretion were identified in 8(8/10) Chinese HIV-1 recombinant subtype B/ C infectors with infected time in 1 year, the specific T lymphocytes are mainly targeted at five seperated peptides. Responses were identified in 17(68%) infectors with infected time more than 3 years, the specific T lymphocytes are mainly targeted at one peptide in p17 and six in p24. There was obviously positive correlation (P = 0.0318, r = 0.519) between the magnitude of responses and viremia in infectors infected time > 3 years. The magnitude of response in infectors infected in 1 year was significantly higher than group infected time > 3 years (P = 0.021). None of healthy individuals produced positive responses.

CONCLUSIONSHIV-1 recombinant subtype B/C Infectors at different stages of diseases recognize different region of gag.

CD4-Positive T-Lymphocytes ; immunology ; virology ; Gene Products, gag ; genetics ; immunology ; HIV Infections ; genetics ; immunology ; virology ; HIV-1 ; classification ; genetics ; immunology ; Humans ; Immunodominant Epitopes ; Interferon-gamma ; genetics ; immunology ; Recombination, Genetic

The prevalence of peanut allergy in Korea is lower than in America. Peanut extract allergens between the two countries have not been standardized. This study was performed to compare the allergenicity of raw Korean and American peanuts with that of roasted peanuts. We prepared the peanut extracts in Korean raw (KP) and roasted peanuts (KRP), and also in American raw (AP) and roasted (ARP) peanuts. We compared the peanut extract allergens of KP, KRP, AP and ARP in vitro with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting, T-cell proliferation assay and skin prick test with sera from peanut-allergic patients. SDS-PAGE and Western blotting demonstrated four allergenic extracts, numerous bands that displayed a high prevalence of IgE binding. IgE-binding bands were at 64, 36 and 17 kDa. Western blot inhibition revealed that either KP or AP could almost completely inhibit the reactivity of the other extract. There were no differences between T-cell proliferation assay and skin prick test. In conclusion, this investigation showed no different allergic components in both raw and roast extracts of Korean and American peanuts.
Allergens/immunology ; Allergens/analysis+ACo- ; Allergens/adverse effects ; Blotting, Western ; Cells, Cultured ; Comparative Study ; Electrophoresis, Polyacrylamide Gel ; Food Hypersensitivity/immunology ; Heat ; Human ; Hybridization ; Korea ; Lymphocyte Transformation ; North America ; Peanuts/immunology ; Peanuts/classification ; Peanuts/chemistry+ACo- ; Plant Extracts/immunology ; Plant Proteins/immunology ; Plant Proteins/analysis+ACo- ; Plant Proteins/adverse effects ; Skin Tests ; Species Specificity ; T-Lymphocytes/immunology ; T-Lymphocytes/drug effects