Messingham Kelly A Nordyke, Badovinac Vladimir P, Harty John T
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
J Immunol. 2003 Oct 15;171(8):4254-62. doi: 10.4049/jimmunol.171.8.4254.
Compared with wild-type (WT) mice, Listeria monocytogenes (LM)-vaccinated perforin-deficient (PKO) mice have elevated levels of CD8(+) T cell memory, but exhibit reduced levels of protection against virulent LM. In this study, Ag-specific CD8(+) T cells from LM-vaccinated WT and PKO mice were used in adoptive transfer assays to determine the contribution of perforin-dependent cytolysis in protective immunity to LM. Perforin deficiency resulted in an approximately 5-fold reduction in the per-cell protective capacity of Ag-specific memory CD8(+) T cells that was not caused by differences in memory cell quality as measured by CD62L/CD27 expression, TCR repertoire use, functional avidity, differences in expansion of Ag-specific cells upon infection, or maintenance of memory levels over time. However, perforin-deficient CD8(+) T cells exhibited reduced in vivo cytotoxic function compared to WT CD8(+) T cells. Consistent with the existence of perforin-independent effector pathways, double-vaccinated PKO mice were as resistant to challenge with LM as single-vaccinated WT mice. Thus, increasing the number of memory CD8(+) T cells can overcome diminished per-cell protective immunity in the absence of perforin.
与野生型（WT）小鼠相比，接种单核细胞增生李斯特菌（LM）的穿孔素缺陷（PKO）小鼠的CD8(+) T细胞记忆水平升高，但对强毒力LM的保护水平降低。在本研究中，将接种LM的WT和PKO小鼠的抗原特异性CD8(+) T细胞用于过继转移试验，以确定穿孔素依赖性细胞溶解在针对LM的保护性免疫中的作用。穿孔素缺陷导致抗原特异性记忆CD8(+) T细胞的单细胞保护能力降低约5倍，这不是由通过CD62L/CD27表达、TCR库使用、功能亲和力、感染后抗原特异性细胞扩增差异或记忆水平随时间维持所测量的记忆细胞质量差异引起的。然而，与WT CD8(+) T细胞相比，穿孔素缺陷的CD8(+) T细胞在体内的细胞毒性功能降低。与存在不依赖穿孔素的效应途径一致，双重接种的PKO小鼠与单次接种的WT小鼠一样对LM攻击具有抗性。因此，在没有穿孔素的情况下，增加记忆CD8(+) T细胞的数量可以克服单细胞保护性免疫的减弱。
