Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation.
The secretion of immunosuppressive factors like interleukin-10 (IL-10), either by tumor cells or by tumor-infiltrating leukocytes, has been recognized as one of the mechanisms involved in tumor immunological escape and a serious obstacle for successful immunotherapy. Therefore, any therapeutic attempts aimed at inducing antitumor immunity in tumor-bearing hosts must overcome this immunosuppressive state. This study aimed to determine whether dendritic cell (DC) immunization, a promising approach to induce antitumor immunity, could break IL-10-induced anergic state in CD4+ T cells, essential cells in generating tumor-specific immunity. We found that the ability of DC to reverse IL-10-induced anergic state in human CD4+ T cells is dependent on the IL-10 concentration that T cells have been exposed to and the degree of DC maturation. The efficacy of mature DC in reversing T cell anergy can be mimicked by higher cell numbers of immature DC. In addition, activated T cells induced by DC stimulation are sensitive to IL-10 treatment. Collectively, our results suggest the use of mature DC and the necessity of antagonizing the action of tumor-derived IL-10 in immunotherapy of cancer with DC immunization.
Chen
M L
ML
Department of Microbiology, Soochow University, Wai Shuang Hsi, Shih Lin, 11102, Taipei, Taiwan, ROC.
Wang
F H
FH
Lee
P K
PK
Lin
C M
CM
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D016753:Interleukin-10