Sex-related differences in regulatory T cell (Treg) function and resistance to B16 melanoma in the absence of B7-H1 co-signaling (40.18)

Autor: Pei Yi Lin, Carolina Livi, Suzanne R Thibodeaux, Margaret E Wierman, Mark Kious, Duane P Jeansonne, Tahiro Shin, Michael J Brumlik, Bin Zhang, Benjamin J Daniel, Tyler J Curiel
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Immunology. 182:40.18-40.18
ISSN: 1550-6606
0022-1767
Popis: We tested Treg function in B7-H1-/- (KO) mice. 6-10 wk male (M) or female (F) KO and M or F wildtype (WT) had equal numbers of CD4+CD25hiFoxP3+ T cells (Tregs) with similar CD25 and Foxp3 MFI. CTLA-4 trended lower in F vs M KO. M and F WT and M KO Tregs suppressed T cell proliferation equally in vitro but F KO Tregs were ~30% less suppressive vs the other 3 groups. Transfer of M KO Tregs fully protected RAG1-/- mice from CD4+RBhi T cell colitis but F KO Tregs did not, with up to 30% weight loss demonstrating poor in vivo Treg function. In M or F WT or KO with subcutaneous B16 melanoma, tumor was different at day 15 in F (159 mm3) vs M (458 mm3, p = 0.04) and F KO vs F WT (593 mm3, p = 0.01). We detected OVA-specific immunity in 0/3 M KO bearing OVA+ B16 vs 3/3 in F KO based on in vivo OT-I cell proliferation. Tregs in pre-pubertal 3-wk F KO had similar phenotype and function vs post-pubertal WT and M KO Tregs. Culture with TGF-β +IL-2 converted 6-wk CD4+CD25- F KO T cells into CD4+CD25hiFoxP3+ T cells with suppression similar to WT, but lower CD25. Thus, F KO T cells can become functional Tregs ex vivo. This previously unknown sex/T cell co-signaling interaction could explain sex-related differences in cancer, autoimmune disease, infection susceptibility and response to hormone antagonists. We hypothesize Treg dysfunction to improve immunity and tumor resistance in KO and estrogen as a B7-H1 co-factor in Treg development. CTLA-4 defects remain undefined. Supported by CA105207, FD003118, and Voelcker and Greehey Trusts
Databáze: OpenAIRE
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