Antigen-specific T cell repertoire modification of CD4+CD25+ regulatory T cells.
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).
Hayashi
Yuki
Y
Department of Immunology and Parasitology, School of Medicine, University of Tokushima, Kuramoto, Tokushima, Japan.
Tsukumo
Shin-ichi
S
Shiota
Hiroshi
H
Kishihara
Kenji
K
Yasutomo
Koji
K
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D010856:Columbidae; D022801:Complementarity Determining Regions / Q000096:biosynthesis; D045304:Cytochromes c / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D007117:Immunization, Secondary; D007156:Immunologic Memory; D018655:Lymphocyte Count; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D000941:Antigens; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta; D045304:Cytochromes c