期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 9, 页码 1819-1834出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20150598
关键词
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资金
- Swiss Vaccine Research Institute
- Swiss National Science Foundation [CRSII3-141789, PP00P3_144883, PP00P3_135442/1, 310030_149340/1]
- European Union (European Research Council) [337043-ProtecTC]
- Swiss National Science Foundation (SNF) [PP00P3_144883, 310030_149340, PP00P3_135442] Funding Source: Swiss National Science Foundation (SNF)
Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition of this chronic phenotype and how it impacts T cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing chronic lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that T cell differentiation and acquisition of a chronic or exhausted phenotype depend critically on the frequency of T cell receptor (TCR) engagement and less significantly on the strength of TCR stimulation. In fact, we noted that low-level antigen exposure promotes the formation of T cells with an acute phenotype in chronic infections. Unexpectedly, we found that T cell populations with an acute or chronic phenotype are maintained equally well in chronic infections and undergo comparable primary and secondary expansion. Thus, our observations contrast with the view that T cells with a typical chronic infection phenotype are severely functionally impaired and rapidly transition into a terminal stage of differentiation. Instead, our data unravel that T cells primarily undergo a form of phenotypic and functional differentiation in the early phase of a chronic LCMV infection without inheriting a net survival or expansion deficit, and we demonstrate that the acquired chronic phenotype transitions into the memory T cell compartment.
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