Yi Zuoan, Stunz Laura L, Lin Wai Wai, Bishop Gail A
Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America.
Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Graduate Immunology Program, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2014 Jul 10;9(7):e102120. doi: 10.1371/journal.pone.0102120. eCollection 2014.
Our laboratory reported previously that TNF receptor associated factor 3 (TRAF3) is a positive regulator of TCR signaling and T cell function. In the current study, we present new findings that reveal differential roles for TRAF3 in the regulation of CD4+ and CD8(+) T cells. In response to TCR stimulation in vitro, TRAF3 has greater impact in CD4(+) T cells than in CD8+ T cells. However, T cell-specific TRAF3 deficient mice (CD4Cre TRAF3(fl°x)/(fl°x); T-TRAF3(-/-)) have a greater number of CD4(+)CD44(hi) effector/memory T cells than littermate control (LMC) mice, possibly due to an inefficient suppressive effect of TRAF3 deficient Foxp3+ regulatory T cells. In contrast, CD8(+)CD44(hi)CD62L(hi) central memory (Tcm) cells are markedly reduced in T-TRAF3(-/-) mice in comparison to LMC mice, although CD8(+)CD44(hi)CD62L(l°w) effector memory T (Tem) cells and naïve T cells (CD8(+)CD44(l°w)CD62L(hi)) do not show significant differences in number. Importantly, TRAF3-deficient Tcm cells exhibit defective homeostasis due to impaired IL-15 signaling. These results indicate that the involvement of TRAF3 in IL-15 mediated signaling to T cells plays a previously unappreciated and critical role in CD8(+) Tcm cell regulation and maintenance.
我们实验室之前报道过，肿瘤坏死因子受体相关因子3（TRAF3）是T细胞受体信号传导和T细胞功能的正向调节因子。在当前研究中，我们展示了新的发现，揭示了TRAF3在调节CD4⁺和CD8⁺ T细胞中具有不同作用。在体外对T细胞受体刺激的反应中，TRAF3对CD4⁺ T细胞的影响比对CD8⁺ T细胞更大。然而，T细胞特异性TRAF3缺陷小鼠（CD4Cre TRAF3（fl°x）/（fl°x）；T - TRAF3（-/-））比同窝对照（LMC）小鼠有更多的CD4⁺CD44（hi）效应/记忆T细胞，这可能是由于TRAF3缺陷的Foxp3⁺调节性T细胞的抑制作用效率低下。相比之下，与LMC小鼠相比，T - TRAF3（-/-）小鼠中的CD8⁺CD44（hi）CD62L（hi）中央记忆（Tcm）细胞明显减少，尽管CD8⁺CD44（hi）CD62L（l°w）效应记忆T（Tem）细胞和幼稚T细胞（CD8⁺CD44（l°w）CD62L（hi））在数量上没有显著差异。重要的是，由于IL - 15信号受损，TRAF3缺陷的Tcm细胞表现出内环境稳态缺陷。这些结果表明，TRAF3参与IL - 15介导的T细胞信号传导在CD8⁺ Tcm细胞的调节和维持中发挥了先前未被认识到的关键作用。
