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
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- 作者：Kazunobu Ohnuki ; Yuri Watanabe ; Yusuke Takahashi ; Sakiko Kobayashi ; Shiho Watanabe ; Shuhei Ogawa ; Motoko Kotani ; Haruo Kozono ; Kazunari Tanabe ; Ryo Abe
- 关键词：Clonal expansion ; Cytokine production ; T cell activation ; CD4+ T cell ; Effector T cell ; Costimulation ; TCR affinity ; Signal transduction
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：20 March 2009
- 年：2009
- 卷：380
- 期：4
- 页码：742-747
- 全文大小：659 K
文摘
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.