Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 8, Pages 5204-5208Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.8.5204
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- Canadian Institute for Health and Research [MOP-53152]
- Canadian Institutes for health Research/Canada Graduate Scholarships Doctoral Award
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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.
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