Van Vu Quang, Darwiche Jinane, Raymond Marianne, Lesage Sylvie, Bouguermouh Salim, Rubio Manuel, Sarfati Marika
Immunoregulation, Centre Hospitalier de l'Université de Montréal, Research Center, l'Hôpital Notre-Dame, Montréal, Québec, Canada.
J Immunol. 2008 Oct 15;181(8):5204-8. doi: 10.4049/jimmunol.181.8.5204.
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.
外周CD103(+)Foxp3(+)调节性T细胞（Tregs）既可以在致耐受性条件下通过同源抗原传递从传统幼稚T细胞发育而来，也可以从胸腺来源的、扩增/分化的天然Tregs发育而来。我们在此表明，造血细胞上自我标记物CD47的表达在稳态下选择性调节CD103(+)Foxp3(+) Treg的稳态。首先，与年龄匹配的对照同窝小鼠相比，在CD47缺陷小鼠（CD47(-/-)）中，效应/记忆样（CD44(高)CD62L(低)）CD103(+)Foxp3(+) Tregs的比例随年龄迅速增加。然而，静止（CD44(低)CD62L(高)）CD103(-)Foxp3(+) Tregs的百分比保持稳定。其次，在CD47(-/-)Foxp3(+) Treg亚群中观察到的增殖率增加（BrdU掺入）仅限于那些表达CD103的Tregs。第三，CD47(-/-) Tregs在体外和体内维持正常的抑制功能，并且它们在老年小鼠中比例的增加导致抗原特异性T细胞反应下降。因此，终生持续表达CD47对于避免CD103(+) Tregs过度扩增至关重要，否则可能会压倒性地抑制抗原特异性T细胞反应。
