Cutting edge: CD47 controls the in vivo proliferation and homeostasis of peripheral CD4+ CD25+ Foxp3+ regulatory T cells that express CD103.
Peripheral CD103(+)Foxp3(+) regulatory T cells (Tregs) can develop both from conventional naive T cells upon cognate Ag delivery under tolerogenic conditions and from thymic-derived, expanded/differentiated natural Tregs. We here show that CD47 expression, a marker of self on hematopoietic cells, selectively regulated CD103(+)Foxp3(+) Treg homeostasis at the steady state. First, the proportion of effector/memory-like (CD44(high)CD62L(low)) CD103(+)Foxp3(+) Tregs rapidly augmented with age in CD47-deficient mice (CD47(-/-)) as compared with age-matched control littermates. Yet, the percentage of quiescent (CD44(low)CD62L(high)) CD103(-)Foxp3(+) Tregs remained stable. Second, the increased proliferation rate (BrdU incorporation) observed within the CD47(-/-)Foxp3(+) Treg subpopulation was restricted to those Tregs expressing CD103. Third, CD47(-/-) Tregs maintained a normal suppressive function in vitro and in vivo and their increased proportion in old mice led to a decline of Ag-specific T cell responses. Thus, sustained CD47 expression throughout life is critical to avoid an excessive expansion of CD103(+) Tregs that may overwhelmingly inhibit Ag-specific T cell responses.
Van
Vu Quang
VQ
Immunoregulation, Centre Hospitalier de l'Université de Montréal, Research Center, l'Hôpital Notre-Dame, Montréal, Québec, Canada.
Darwiche
Jinane
J
Raymond
Marianne
M
Lesage
Sylvie
S
Bouguermouh
Salim
S
Rubio
Manuel
M
Sarfati
Marika
M
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D015703:Antigens, CD; D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; C091367:alpha E integrins