Takeshi Kawabe

Associate Professor, Graduate School of Medicine, Tohoku University *Profile is at the time of the award.

2022Inamori Research GrantsBiology & Life sciences

Research topics
Developing a novel therapeutic strategy to infectious diseases based on innate immune function of T lymphocytes
T lymphocytes play an essential role in adaptive immunity. Within this population, we have recently found a novel "Memory-phenotype (MP) cells" possessing innate immune function. This study aims to clarify how MP cells are generated and maintained in steady state as well as what immunological functions they have in host defense.


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Outline of Research Achievments

CD4 T lymphocytes play essential roles in adaptive immunity. In 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, Gata3(hi) 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. Based on these hypotheses, this study aimed at identifying markers that can distinguish MP from conventional, foreign antigen-specific memory cells, dissecting mechanisms that govern MP cell differentiation in steady state, and clarifying their innate immune function in host defense.

In the present study, we found that MP CD4 T lymphocytes can be distinguished from antigen-specific memory cells using markers CD127, Sca1, and Bcl2 and that MP cells themselves can be divided into four subpopulations (i.e., CD127(hi) Sca1(lo), CD127(hi) Sca1(hi), CD127(lo) Sca1(hi), and CD127(lo) Sca1(lo)). We also found that among these MP subpopulations, CD127(lo) Sca1(lo-hi) subsets represent proliferating, immature MP cells whereas CD127(hi) Sca1(hi) cells are the most differentiated, mature MP cells. Furthermore, our data suggest that the CD127(hi) Sca1(hi) subset adopts an MP1-like phenotype and exhibits the highest reactivity to cytokines IL-12/18/2. Together these results identify CD127(hi) Sca1(hi) T-bet(+) MP1 cells as an innate-like CD4 T lymphocyte population that can be stimulated with Th1-type cytokines. Based on these observations we propose “immune-stimulating therapy” by enhancing innate immune activity of MP cells in host defense.

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Biology & Life sciences