Johnson Lexus R, Weizman Orr-El, Rapp Moritz, Way Sing Sing, Sun Joseph C
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Cell Rep. 2016 Oct 11;17(3):636-644. doi: 10.1016/j.celrep.2016.09.019.
Despite robust secondary T cell expansion primed by vaccination, the impact on primary immune responses to heterotypic antigens remains undefined. Here we show that secondary expansion of epitope-specific memory CD8 T cells primed by prior infection with recombinant pathogens limits the primary expansion of naive CD8 T cells with specificity to new heterologous antigens, dampening protective immunity against subsequent pathogen challenge. The degree of naive T cell repression directly paralleled the magnitude of the recall response. Suppressed primary T cell priming reflects competition for antigen accessibility, since clonal expansion was not inhibited if the primary and secondary epitopes were expressed on different dendritic cells. Interestingly, robust recall responses did not impact antigen-specific NK cells, suggesting that adaptive and innate lymphocyte responses possess different activation requirements or occur in distinct anatomical locations. These findings have important implications in pathogen vaccination strategies that depend on the targeting of multiple T cell epitopes.
尽管疫苗接种引发了强劲的继发性T细胞扩增，但对异型抗原的原发性免疫反应的影响仍不明确。在这里，我们表明，先前感染重组病原体引发的表位特异性记忆CD8 T细胞的继发性扩增限制了对新的异源抗原具有特异性的幼稚CD8 T细胞的原发性扩增，削弱了对后续病原体攻击的保护性免疫。幼稚T细胞抑制的程度与回忆反应的强度直接平行。原发性T细胞启动受抑制反映了对抗原可及性的竞争，因为如果原发性和继发性表位在不同的树突状细胞上表达，克隆扩增就不会受到抑制。有趣的是，强劲的回忆反应不会影响抗原特异性NK细胞，这表明适应性和先天性淋巴细胞反应具有不同的激活要求或发生在不同的解剖位置。这些发现对依赖于多个T细胞表位靶向的病原体疫苗接种策略具有重要意义。
