Armitage Ellis, Quan Diana, Flórido Manuela, Palendira Umaimainthan, Triccas James A, Britton Warwick J
Centenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Vaccines (Basel). 2023 Sep 29;11(10):1549. doi: 10.3390/vaccines11101549.
is a major human pathogen, and new vaccines are needed to prevent transmission. Mucosal vaccination may confer protection against by stimulating tissue-resident memory (T) CD4 T cells in the lungs. The chemokine receptor CXCR3 promotes lung recruitment of T cells, but its role in T development is unknown. This study demonstrates the recombinant influenza A virus vaccine PR8.p25, expressing the immunodominant T cell epitope p25, induces CXCR3 expression on p25-specific CD4 T cells in the lungs so that the majority of vaccine-induced CD4 T expresses CXCR3 at 6 weeks. However, CXCR3 mice developed equivalent antigen-specific CD4 T cell responses to wild-type (WT) mice following PR8.p25, and surprisingly retained more p25-specific CD4 T in the lungs than WT mice at 6 weeks. The adoptive transfer of CXCR3 and WT P25 T cells into WT mice revealed that the initial recruitment of vaccine-induced CD4 T cells into the lungs was independent of CXCR3, but by 6 weeks, CXCR3-deficient P25 T cells, and especially CXCR3 T, were significantly reduced compared to CXCR3-sufficient P25 T cells. Therefore, although CXCR3 was not essential for CD4 T recruitment or retention, it provided a competitive advantage for the induction of -specific CD4 T in the lungs following pulmonary immunization.
是一种主要的人类病原体，需要新的疫苗来预防传播。黏膜疫苗接种可能通过刺激肺部组织驻留记忆（T）CD4 T细胞来提供针对的保护。趋化因子受体CXCR3促进T细胞向肺部募集，但其在T细胞发育中的作用尚不清楚。本研究表明，表达免疫显性T细胞表位p25的重组甲型流感病毒疫苗PR8.p25可诱导肺部p25特异性CD4 T细胞上CXCR3的表达，因此大多数疫苗诱导的CD4 T细胞在6周时表达CXCR3。然而，CXCR3基因敲除小鼠在接种PR8.p25后对野生型（WT）小鼠产生了相当的抗原特异性CD4 T细胞反应，并且令人惊讶的是，在6周时其肺部保留的p25特异性CD4 T细胞比WT小鼠更多。将CXCR3基因敲除和WT的P25 T细胞过继转移到WT小鼠中发现，疫苗诱导的CD4 T细胞最初向肺部的募集与CXCR3无关，但到6周时，与CXCR3充足的P25 T细胞相比，CXCR3缺陷的P25 T细胞，尤其是CXCR3基因敲除的T细胞显著减少。因此，尽管CXCR3对于CD4 T细胞的募集或保留不是必需的，但它为肺部免疫后诱导特异性CD4 T细胞提供了竞争优势。
