B7-deficient autoreactive T cells are highly susceptible to suppression by CD4(+)CD25(+) regulatory T cells.
CD4(+)CD25(+) regulatory T cells (Tregs) suppress immunity to infections and tumors as well as autoimmunity and graft-vs-host disease. Since Tregs constitutively express CTLA-4 and activated T cells express B7-1 and B7-2, it has been suggested that the interaction between CTLA-4 on Tregs and B7-1/2 on the effector T cells may be required for immune suppression. In this study, we report that autopathogenic T cells from B7-deficient mice cause multiorgan inflammation when adoptively transferred into syngeneic RAG-1-deficient hosts. More importantly, this inflammation is suppressed by adoptive transfer of purified wild-type (WT) CD4(+)CD25(+) T cells. WT Tregs also inhibited lymphoproliferation and acquisition of activation markers by the B7-deficient T cells. An in vitro suppressor assay revealed that WT and B7-deficient T cells are equally susceptible to WT Treg regulation. These results demonstrate that B7-deficient T cells are highly susceptible to immune suppression by WT Tregs and refute the hypothesis that B7-CTLA-4 interaction between effector T cells and Tregs plays an essential role in Treg function.
May
Kenneth F
KF
Department of Pathology, Divisions of Cancer Immunology and Dermatology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA.
Chang
Xing
X
Zhang
Huiming
H
Lute
Kenneth D
KD
Zhou
Penghui
P
Kocak
Ergun
E
Zheng
Pan
P
Liu
Yang
Y
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D007108:Immune Tolerance; D007249:Inflammation; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000502:physiology* / Q000637:transplantation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse