Constitutive expression of IL-7 receptor α does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection

Constitutive expression of IL-7 receptor α does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection
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DOI:
10.4049/jimmunol.180.5.2855
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发表时间:
2008-03-01
影响因子:
4.4
通讯作者:
Harty, John T.
Harty, John T.
中科院分区:
医学2区
文献类型:
--
作者:
Haring, Jodie S.;Jing, Xuefang;Harty, John T.

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IL-7 R α(CD 127)的表达已被认为是记忆T细胞前体存活的主要决定因素。我们研究了单核细胞增生李斯特菌感染后,T细胞上IL-7 R α的组成型表达是否增加了内源性Ag特异性CD 4和CD 8 T细胞的扩增和/或减少了其收缩。结果表明,单独IL-7 Ra的组成型表达不足以赋予响应感染的CD 8 T细胞扩增或存活优势,并且与野生型对照中观察到的那些相比,不增加记忆性CD 8 T细胞数量。IL-7 R α的组成性表达确实允许Ag特异性CD 4 T细胞稍微延长扩增时间;然而,它并没有改变收缩期或防止感染后后期记忆T细胞数量的减少。在IL-7 R α转基因小鼠中产生的记忆性CD 4和CD 8 T细胞在二次感染后与野生型T细胞类似地扩增,并且免疫的IL-7 R α转基因小鼠完全免受致死性细菌攻击,这表明IL-7 R α的组成型表达不损害或显著改善记忆/二次效应或T细胞功能。这些结果表明,单独表达IL-7 R α不支持效应Ag特异性CD 4或CD 8 T细胞在细菌感染后进入记忆期的存活增加。
Expression of IL-7R alpha (CD127) has been suggested as a major determinant in the survival of memory T cell precursors. We investigated whether constitutive expression of IL-7R alpha on T cells increased expansion and/or decreased contraction of endogenous Ag-specific CD4 and CD8 T cells following infection with Listeria monocytogenes. The results indicate that constitutive expression of IL-7Ra alone was not enough to impart an expansion or survival advantage to CD8 T cells responding to infection, and did not increase memory CD8 T cell numbers over those observed in wild-type controls. Constitutive expression of IL-7R alpha did allow for slightly prolonged expansion of Ag-specific CD4 T cells; however, it did not alter the contraction phase or protect against the waning of memory T cell numbers at later times after infection. Memory CD4 and CD8 T cells generated in IL-7R alpha transgenic mice expanded similarly to wild-type T cells after secondary infection, and immunized IL-7Ra transgenic mice were fully protected against lethal bacterial challenge demonstrating that constitutive expression of IL-7R alpha does not impair, or markedly improve memory/secondary effect-or T cell function. These results indicate that expression of IL-7R alpha alone does not support increased survival of effector Ag-specific CD4 or CD8 T cells into the memory phase following bacterial infection.