Antigen-specific CD4 effector T cells: Analysis of factors regulating clonal expansion and cytokine production: Clonal expansion and cytokine production by CD4 effector T cells |
| |
Authors: | Kazunobu Ohnuki Yusuke Takahashi Shiho Watanabe Motoko Kotani Kazunari Tanabe |
| |
Affiliation: | a Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan b Department of Urology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan |
| |
Abstract: | In order to fully understand T cell-mediated immunity, the mechanisms that regulate clonal expansion and cytokine production by CD4+ antigen-specific effector T cells in response to a wide range of antigenic stimulation needs clarification. For this purpose, panels of antigen-specific CD4+ T cell clones with different thresholds for antigen-induced proliferation were generated by repeated stimulation with high- or low-dose antigen. Differences in antigen sensitivities did not correlate with expression of TCR, CD4, adhesion or costimulatory molecules. There was no significant difference in antigen-dependent cytokine production by TG40 cells transfected with TCR obtained from either high- or low-dose-responding T cell clones, suggesting that the affinity of TCRs for their ligands is not primary determinant of T cell antigen reactivity. The proliferative responses of all T cell clones to both peptide stimulation and to TCRβ crosslinking revealed parallel dose-response curves. These results suggest that the TCR signal strength of effector T cells and threshold of antigen reactivity is determined by an intrinsic property, such as the TCR signalosome and/or intracellular signaling machinery. Finally, the antigen responses of high- and low-peptide-responding T cell clones reveal that clonal expansion and cytokine production of effector T cells occur independently of antigen concentration. Based on these results, the mechanisms underlying selection of high “avidity” effector and memory T cells in response to pathogen are discussed. |
| |
Keywords: | Clonal expansion Cytokine production T cell activation CD4+ T cell Effector T cell Costimulation TCR affinity Signal transduction |
本文献已被 ScienceDirect 等数据库收录! |
|