Apoptosis ; Proteins/metabolism* ; Mitochondria/metabolism* ; CD4-Positive T-Lymphocytes

Humans ; CD4-Positive T-Lymphocytes/metabolism* ; CD8-Positive T-Lymphocytes/metabolism* ; HIV Infections/drug therapy* ; HIV-1

Animals ; CD4 Antigens ; blood ; CD4-Positive T-Lymphocytes ; metabolism ; radiation effects ; CD8 Antigens ; blood ; CD8-Positive T-Lymphocytes ; metabolism ; radiation effects ; Male ; Mice ; Ultraviolet Rays

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

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a pathologically similar disease used to model MS in rodents, are typical CD4+ T cell-dominated autoimmune diseases. CD4+ interleukin (IL)17+ T cells (Th17 cells) have been well studied and have shown that they play a critical role in the pathogenesis of MS/EAE. However, studies have suggested that CD8+IL17+ T cells (Tc17 cells) have a similar phenotype and cytokine and transcription factor profiles to those of Th17 cells and have been found to be crucial in the pathogenesis of autoimmune diseases, including MS/EAE, psoriasis, type I diabetes, rheumatoid arthritis, and systemic lupus erythematosus. However, the evidence for this is indirect and insufficient. Therefore, we searched for related publications and attempted to summarize the current knowledge on the role of Tc17 cells in the pathogenesis of MS/EAE, as well as in the pathogenesis of other autoimmune diseases, and to find out whether Tc17 cells or Th17 cells play a more critical role in autoimmune disease, especially in MS and EAE pathogenesis, or whether the interaction between these two cell types plays a critical role in the development of the disease.
Animals ; Mice ; Encephalomyelitis, Autoimmune, Experimental ; Th17 Cells ; CD8-Positive T-Lymphocytes/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Multiple Sclerosis/metabolism* ; Mice, Inbred C57BL

T lymphocytes are an integral part of the effective immune response against various tumors, but they are frequently functionally unresponsive in tumor-bearing patients. This study was aimed to investigate the T lymphocyte function of patients with acute myeloid leukemia (AML) in different status through analyzing intracellular cytokine characteristics of T lymphocytes in AML patients. The T lymphocytes from 18 de nuevo AML patients in different status and 10 healthy controls were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the presence of monensin, and were stained with fluorescent McAbs CD4-PITC, CD8-FITC and IFNgamma-PE, ILA-PE, then their T lymphocytes were analyzed by flow cytometry. The results showed that IFN-gamma level in CD4+ and CD8+ T cells of de novo AML patients was significantly lower as compared with healthy controls (p<0.05), while IL-4 level in CD4+ and CD8+ T cells was low too, there was no significant difference between de novo AML patients and healthy controls. In AML patients in clinical remission, IFNgamma level in CD8+ T cells was significantly higher than that in de novo AML patients (p<0.05), but there was no significant difference as compared with healthy controls (p>0.05). In relapsed AML patients, IFNgamma level in CD4+ and CD8+ T cells was significantly lower than that in healthy controls and in AML patients with CR (p<0.05), while IL-4 level was significantly higher than that in healthy controls and de nuevo AML patients (p<0.05). It is concluded that the cytokine secretion in T cell subsets of AML patients in different status is changed. Correspondingly, the Th1/Tc1 level is low after stimulating CD4+ and CD8+ T cells in peripheral blood of de novo AML patients, but not different from healthy controls. Though the Th1 level in T cells of AML patients in complete remission is low, but Tc1 response is even enhanced as high as the healthy controls. The Th2/Tc2-like response of CD4+ and CD8+ T cells in relapsed AML patients obviously increases when compared with Th1/Tc1-like response.
CD4-Positive T-Lymphocytes ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Humans ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; Leukemia, Myeloid, Acute ; immunology

This study aims to investigate the effect of anti-PD-1 antibody expressed in mouse mammary gland on the surface antigen protein of spleen T cells, cytokine expression, spleen CD4⁺ T cell proliferation and proliferation related pathways of transgenic mice at the cellular level. Transgenic mice expressing anti-human PD-1 antibody at 8 weeks of age without pregnancy and 18 weeks of age with lactation were divided into two groups, with transgenic negative mice in each group as the control. Spleen lymphocytes were extracted and the changes of spleen lymphocytes were detected. Compared with transgenic negative mice, the proportion of effector T cells of spleen T cells in the immune system of transgenic mice with anti-PD-1 antibody expressed in breast increased, the proportion of Treg cells decreased, and the IFN-γ, IL-17 and IL-2 expressed in CD4⁺ T cells increased in varying degrees. Moreover, IL-4, IL-10 and TGF-β in CD4⁺ T cells did not change, nor did some cell surface protein molecules related to T cell stimulate. There was no significant difference in T cell proliferation between transgenic positive and transgenic negative mice. In transgenic positive mice, the expression of phosphorylated proteins in PI3K/Akt/mTOR and RAS/MEK/ERK pathways were partially up-regulated, but the whole pathway was not completely up-regulated. Therefore, it is feasible to use transgenic mice as host to express monoclonal antibodies related to immune system such as anti-PD-1 antibody.
Mice ; Animals ; Female ; Mice, Transgenic ; Spleen/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cytokines/metabolism*

BACKGROUNDSystemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4(+)CD25(+) Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis.

METHODSTh17s (CD4 and IL-17 positive) and CD4(+)CD25(+) Tregs (CD4, CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score (MRSS), anti-topoisomerase I antibody, anti-U1 ribonucleoprotein (RNP) antibody, systemic involvements, pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols. The correlations between the experimental and clinical data were investigated.

RESULTSThe ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74% vs. 4.41%, P < 0.001). The amount of Th17 was positively correlated with disease duration (R = 0.531, P = 0.013) and duration of the second symptoms (R = 0.505, P = 0.023). The ratio of CD4(+)CD25(+) Treg in SSc patients also significantly differed from the healthy controls (3.04% vs. 2.24%, P = 0.018). Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12, P = 0.043). Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11, P = 0.042).

CONCLUSIONST cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4(+)CD25(+) Tregs also proliferate in SSc and may play important roles in promoting fibrosis.

CD4-Positive T-Lymphocytes ; metabolism ; Cells, Cultured ; Flow Cytometry ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Scleroderma, Systemic ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology ; metabolism ; Th17 Cells ; metabolism

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4⁺ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease. METHODS: From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI. CONCLUSIONS In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.
Humans ; Leukocytes, Mononuclear ; Lupus Erythematosus, Systemic/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; DNA Repair ; RNA, Messenger/metabolism*

Adult ; Aged ; CD4-Positive T-Lymphocytes ; Case-Control Studies ; Female ; Humans ; Interleukin-17 ; blood ; Liver Cirrhosis, Biliary ; blood ; immunology ; metabolism ; Male ; Middle Aged ; T-Lymphocytes, Helper-Inducer