BACKGROUND: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8 METHODS: For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8 RESULTS: IL-15 addition partially reversed the decrease in CD3 CONCLUSION These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.
Asbestos/adverse effects* ; CD8-Positive T-Lymphocytes/metabolism* ; Humans ; Interleukin-15/pharmacology* ; Lymphocyte Activation/immunology* ; T-Lymphocytes, Cytotoxic/metabolism*

CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) have been implicated in suppressing T cell immune responses to hepatitis B virus (HBV), but the inhibition mechanism has not being clear yet. This study investigated the effects of soluble FGL2 (sFGL2) secreted by Tregs on immune suppression in chronic HBV-infected patients. We verified that sFGL2 protein and mRNA were highly expressed in Tregs. The separated Tregs by using magnetic beads from peripheral blood mononuclear cells (PBMCs) in 20 patients with chronic hepatitis B were co-cultured with PBMCs at a ratio of 1:3 with anti-CD3 stimulating antibody or FGL2 blocking antibody. The proliferation index of CD8(+)T cells after blocking FGL2 was higher than that in blank group (3.58±0.18 vs. 3.28±0.17, P=0.034) in 18 of 20 samples, and lower than that in CD3 stimulation group (3.82±0.19, P=0.026) in 16 of 20 samples. The IFN-γ secreted in the mixed culture in the absence of Tregs was higher than that in the culture in the presence of Tregs, but it could be abolished by FGL2 blocking antibody. These results suggest that sFGL2 protein secreted by Tregs suppresses the proliferation and function of CD8(+) T cells in chronic hepatitis B.
CD8-Positive T-Lymphocytes ; immunology ; metabolism ; Cells, Cultured ; Fibrinogen ; immunology ; metabolism ; Hepatitis B, Chronic ; immunology ; metabolism ; Humans ; T-Lymphocytes, Regulatory ; immunology ; metabolism

Aplastic anemia(AA) is mostly considered as an immune-mediated bone marrow failure syndrome, characterized by pancytopenia and bone marrow hypoplasia. The pathogenesis of AA is complicated, until now it is not fully understood. Further study on the pathological mechanism will be helpful for the diagnosis and treatment of AA. CD8(+) T cells and their secreted cytokines play important roles in the abnormal immunity during the process of AA. Thus, this review focuses on the role of CD8(+) T cells and their secreted cytokines in the pathogenesis of AA.
Anemia, Aplastic ; immunology ; metabolism ; pathology ; CD8-Positive T-Lymphocytes ; immunology ; metabolism ; secretion ; Cytokines ; metabolism ; Humans ; Immunity, Cellular

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

In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+T cells rapidly fall into anergy to host cells, while donor CD4+T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+regulatory T cells (T(reg) cells) are critical in maintaining the donor CD8+T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T(reg) cells in determining cGVHD versus aGVHD.
T-Lymphocytes, Regulatory/*immunology ; Mice, Inbred DBA ; Mice ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Immune Tolerance/physiology ; Graft vs Host Disease/*immunology ; Female ; Clonal Anergy/*physiology ; Chronic Disease ; CD8-Positive T-Lymphocytes/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Animals

OBJECTIVE: To investigate the relationship between immune status of adenoids and secretory otitis media (SOM). METHOD: The adenoid tissue samples of 72 cases with SOM and 30 cases with adenoid hypertrophy without SOM were studied by immunohistochemical method. RESULT: The PCNA, BCL-2, CD4+, CD8+ and CD4+ / CD8+ in SOM tissue samples were 30.85 +/- 1.73, 21.27 +/- 1.25, 41.90 +/- 9.07, 20.45 +/- 7.08 and 2.10 +/- 0.17, respectively, which were much more than that of tissue samples without SOM (25.25 +/- 1.75, 14.05 +/- 1.02, 16.30 +/- 8.21, 11.15 +/- 5.71, 1.39 +/- 0.15 respectively) (P < 0.01). The expression of CD4+ in T-lymphocyte was obviously higher than that of CD8+. CONCLUSION In adenoid tissues of SOM patients, the activity of T-lymphocyte subsets are increased,the adenoids are enlarged and local immunity are enhanced. Therefore,adenoidectomy should be applied in SOM patients as early as possible.
Adenoids ; immunology ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Otitis Media with Effusion ; immunology ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

CD8-Positive T-Lymphocytes ; metabolism ; Case-Control Studies ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; biosynthesis ; Lymphocytes ; immunology ; Oligodeoxyribonucleotides ; pharmacology

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis

Adult ; Animals ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Hepatitis B, Chronic ; immunology ; metabolism ; Humans ; Leukocyte Common Antigens ; biosynthesis ; genetics ; Liver Neoplasms ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged

PURPOSE: To identify new immunogenic HLA-A*33;03-restricted epitopes from the human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical cancer. MATERIALS AND METHODS: We synthesized fourteen overlapping 15-amino acid peptides and measured intracellular interferon-γ (IFN-γ) production in PBMC and CD8+ cytotoxic T lymphocytes (CTLs) after sensitization with these peptides using flow cytometry and ELISpot assay. The immunogenicity of epitopes was verified using a ⁵¹Cr release assay with SNU1299 cells. RESULTS: Among the fourteen 15-amino acid peptides, E7₄₉₋₆₃ (RAHYNIVTFCCKCDS) demonstrated the highest IFN-γ production from peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with E7₄₉₋₆₃ showed higher cytotoxic effect against SNU1299 cells than did CD8+ CTLs sensitized with other peptides or a negative control group. Thirteen 9- or 10-amino acid overlapping peptides spanning E7₄₉₋₆₃, E7₅₀₋₅₉ (AHYNIVTFCC), and E7₅₂₋₆₁ (YNIVTFCCKC) induced significantly higher IFN-γ production and cytotoxic effects against SNU1299 cells than the other peptides and negative controls, and the cytotoxicity of E7₅₀₋₅₉- and E7₅₂₋₆₁-sensitized PBMCs was induced via the cytolytic effect of CD8+ CTLs. CONCLUSION: We identified E7₅₀₋₅₉ and E7₅₂₋₆₁ as novel HPV 16 E7 epitopes for HLA-A*33;03. CD8+ CTL sensitized with these peptides result in an antitumor effect against cervical cancer cells. These epitopes could be useful for immune monitoring and immunotherapy for cervical cancer and HPV 16-related diseases including anal cancer and oropharyngeal cancer.
Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Epitopes/*immunology/therapeutic use ; Female ; *HLA-A Antigens ; Human papillomavirus 16/*immunology ; Humans ; *Immunotherapy ; Interferon-gamma/analysis/*biosynthesis ; Leukocytes, Mononuclear/immunology/metabolism ; T-Lymphocytes, Cytotoxic/immunology/metabolism ; Uterine Cervical Neoplasms/*therapy