Ge Qing, Bai Ailin, Jones Brendan, Eisen Herman N, Chen Jianzhu
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3041-6. doi: 10.1073/pnas.0307339101. Epub 2004 Feb 19.
To study competition between naïve and memory T cells, we examined proliferation of adoptively transferred naïve CD8(+) T cells in lymphopenic recipients or recipients containing a clonal population of CD8(+) T cells. We find a hierarchy in the extent of T cell proliferation that appears to correlate with the strength of T cell receptor (TCR)-self-peptide-MHC (pepMHC) interactions. CD8(+) T cells also proliferate in recipients containing a full complement of CD8(+) cells with a different TCR if the transferred T cells experience stronger TCR-self-pepMHC interactions than the resident T cells. Furthermore, CD8(+) T cells proliferate in recipients that contain memory CD8(+) cells with a different TCR, but in this case the relative strengths of TCR-self-pepMHC interactions are not as critical. In contrast, CD8(+) T cells do not proliferate significantly in recipients harboring naïve or memory CD8(+) cells that bear the same TCR as the transferred cells. These results suggest that, among naïve T cells and between naïve and memory T cells, CD8(+) cells having the same TCR compete for both self-pepMHC and cytokines, whereas TCR-different CD8(+) cells compete for cytokines. These competitive relationships probably help maintain the size and TCR diversity of naïve and memory T cell populations required for optimal immune responses.
为了研究初始T细胞与记忆T细胞之间的竞争，我们检测了过继转移的初始CD8(+) T细胞在淋巴细胞减少的受体或含有克隆性CD8(+) T细胞群体的受体中的增殖情况。我们发现T细胞增殖程度存在等级差异，这似乎与T细胞受体（TCR）-自身肽-MHC（肽-MHC）相互作用的强度相关。如果转移的T细胞比驻留T细胞经历更强的TCR-自身肽-MHC相互作用，CD8(+) T细胞也会在含有具有不同TCR的完整CD8(+)细胞群体的受体中增殖。此外，CD8(+) T细胞会在含有具有不同TCR的记忆CD8(+)细胞的受体中增殖，但在这种情况下，TCR-自身肽-MHC相互作用的相对强度并不那么关键。相比之下，CD8(+) T细胞在含有与转移细胞具有相同TCR的初始或记忆CD8(+)细胞的受体中不会显著增殖。这些结果表明，在初始T细胞之间以及初始T细胞与记忆T细胞之间，具有相同TCR的CD8(+)细胞会竞争自身肽-MHC和细胞因子，而具有不同TCR的CD8(+)细胞则竞争细胞因子。这些竞争关系可能有助于维持最佳免疫反应所需的初始和记忆T细胞群体的大小以及TCR多样性。
