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Antigen-Specific T Cell Repertoire Modification of CD4⁺CD25⁺ Regulatory T Cells¹

Yuki Hayashi^*,, Shin-ichi Tsukumo^*, Hiroshi Shiota, Kenji Kishihara^* and Koji Yasutomo^2,*

Departments of ^* Immunology and Parasitology, and Ophthalmology and Visual Neuroscience, School of Medicine, University of Tokushima, Tokushima, Japan

T cell immune responses are regulated by the interplay between effector and suppressor T cells. Immunization with Ag leads to the selective expansion and survival of effector CD4⁺ T cells with high affinity TCR against the Ag and MHC. However, it is not known if CD4⁺CD25⁺ regulatory T cells (T_reg) recognize the same Ag as effector T cells or whether Ag-specific TCR repertoire modification occurs in T_reg. In this study, we demonstrate that after a primary Ag challenge, T_reg proliferate and TCR repertoire modification is observed although both of these responses were lower than those in conventional T cells. The repertoire modification of Ag-specific T_reg after primary Ag challenge augmented the total suppressive function of T_reg against TCR repertoire modification but not against the proliferation of memory CD4⁺ T cells. These results reveal that T cell repertoire modification against a non-self Ag occurs in T_reg, which would be crucial for limiting excess primary and memory CD4⁺ T cell responses. In addition, these studies provide evidence that manipulation of Ag-specific T_reg is an ideal strategy for the clinical use of T_reg.

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