東北大学大学院医学系研究科病理病態学講座免疫学分野Tohoku University Graduate School of Medicine― 114 ―CD4+ T lymphocytes play essential roles in adaptive immunity. Within this population, we previously reported a novel “memory-phenotype (MP)” cell subpopulation. MP cells develop from peripheral naïve precursors in steady state, and can exert innate effector function in pathogen infection. Moreover, we recently found the possibility that the same cells comprise T-bet+ MP1, Gata3hi MP2, and Rorgt+ MP17 subsets. These observations suggest that each MP subset has distinct differentiation as well as activation mechanisms to contribute to host defense. On the other hand, it is also possible that based on their self-reactivity, MP cells have a potential to induce autoimmune or inflammatory disease. Based on these hypotheses, this study aimed at characterizing the biology of MP cells, dissecting mechanisms that govern MP cell differentiation in steady state, and clarifying immunological functions of MP cells in host defense and autoimmunity.In the present study, we found that MP CD4+ T lymphocytes can be divided into four subpopulations: CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo. We also found that among these MP subpopulations, the CD127hi Sca1hi subset adopts an MP1-like phenotype and exhibits the highest reactivity to cytokines IL-12/18/2. Furthermore, we showed that MP1 cells can promote host survival in Toxoplasma infection in the absence of antigen recognition and that this innate-like activity can be significantly enhanced by treatment with exogenous IL-12. On the other hand, we also found that when transferred into immunodeficient mice, MP1 cells can induce multi-organ inflammation in an IL-12-dependent manner.Together our results identify CD127hi Sca1hi T-bet+ MP1 cells as an innate-like CD4+ T lymphocyte population that can be stimulated with IL-12. Based on these observations, we propose “immune-stimulating therapy” by enhancing innate immune activity of MP cells in host defense while inhibiting their AbstractDeveloping a new therapeutic strategy to infectious disease 新規の自然免疫型Tリンパ球を標的とした新たな感染症治療戦略の創出by targeting novel innate T lymphocytes河部 剛史Takeshi Kawabe
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