Kim Sung-Kwon, Brehm Michael A, Welsh Raymond M, Selin Liisa K
Department of Pathology, University of Massachusetts, Worcester, MA 01655, USA.
J Immunol. 2002 Jul 1;169(1):90-8. doi: 10.4049/jimmunol.169.1.90.
By examining adoptively transferred CSFE-labeled lymphocytic choriomeningitis virus (LCMV)-immune donor T cells in Thy-1 congenic hosts inoculated with viruses or with the cytokine inducer poly(I:C), strikingly different responses of bona fide memory T cells were found in response to different stimuli. Poly(I:C) (cytokine) stimulation caused a limited synchronized division of memory CD8 T cells specific to each of five LCMV epitopes, with no increase and sometimes a loss in number, and no change in their epitope hierarchy. Homologous LCMV infection caused more than seven divisions of T cells specific for each epitope, with dramatic increases in number and minor changes in hierarchy. Infections with the heterologous viruses Pichinde and vaccinia (VV) caused more than seven divisions and increases in number of T cells specific to some putatively cross-reactive but not other epitopes and resulted in substantial changes in the hierarchy of the LCMV-specific T cells. Hence, there can be memory T cell division without proliferation (i.e., increase in cell number) in the absence of Ag and division with proliferation in the presence of Ag from homologous or heterologous viruses. Heterologous protective immunity between viruses is not necessarily reciprocal, given that LCMV protects against VV but VV does not protect against LCMV. VV elicited proliferation of LCMV-induced CD8 and CD4 T cells, whereas LCMV did not elicit proliferation of VV-induced T cells. Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity.
通过检测在接种病毒或细胞因子诱导剂聚肌胞苷酸（poly(I:C)）的Thy-1同基因宿主中过继转移的羧基荧光素二乙酸琥珀酰亚胺酯（CSFE）标记的淋巴细胞性脉络丛脑膜炎病毒（LCMV）免疫供体T细胞，发现真正的记忆T细胞对不同刺激的反应截然不同。聚肌胞苷酸（细胞因子）刺激导致针对五个LCMV表位中每个表位的记忆性CD8 T细胞进行有限的同步分裂，细胞数量没有增加，有时还会减少，且其表位层次没有变化。同源LCMV感染导致针对每个表位的T细胞进行超过七次分裂，细胞数量显著增加，层次有微小变化。感染异源病毒皮钦德病毒和痘苗病毒（VV）导致针对一些推测为交叉反应性表位而非其他表位的T细胞进行超过七次分裂且数量增加，并导致LCMV特异性T细胞的层次发生实质性变化。因此，在没有抗原的情况下，记忆T细胞可以分裂但不增殖（即细胞数量增加），而在存在同源或异源病毒抗原的情况下，记忆T细胞分裂并增殖。鉴于LCMV可预防VV，但VV不能预防LCMV，病毒之间的异源保护性免疫不一定是相互的。VV引发LCMV诱导的CD8和CD4 T细胞增殖，而LCMV不引发VV诱导的T细胞增殖。因此，根据病原体和感染顺序，异源病原体可能以与异源免疫一致的模式选择性地刺激记忆库。
