CD44 expression positively correlates with Foxp3 expression and suppressive function of CD4.sup.+ .sup.T.sub.reg cells

• Published in: Biology direct 2009-10, Vol.4, p.40
• Main Authors: Liu, Tie, Soong, Lynn, Liu, Gang, König, Rolf, Chopra, Ashok K
• Format: Article
• Language: English
• Subjects: CD4 lymphocytes; Gene expression; Histocompatibility; Physiological aspects; Transforming growth factors
• ISSN: 1745-6150; 1745-6150
• DOI: 10.1186/1745-6150-4-40

CD4.sup.+.sup.CD25.sup.+ .sup.regulatory T (T.sub.reg ) cells develop in the thymus and can suppress T cell proliferation, modulated by Foxp3 and cytokines; however, the relevance of CD44 in T.sub.reg cell development is less clear. To address this issue, we analyzed Foxp3 expression in CD44.sup.+ .sup.T.sub.reg cells by using multiple parameters, measured the levels of the immunoregulatory cytokine interleukin (IL)-10 in various thymocyte subsets, and determined the suppressor activity in different splenic T.sub.reg cell populations. Within mouse thymocytes, we detected T.sub.reg cells with two novel phenotypes, namely the CD4.sup.+.sup.CD8.sup.-.sup.CD25.sup.+.sup.CD44.sup.+ .sup.and CD4.sup.+.sup.CD8.sup.-.sup.CD25.sup.+.sup.CD44.sup.- .sup.staining features. Additional multi-parameter analyses at the single-cell and molecular levels suggested to us that CD44 expression positively correlated with Foxp3 expression in thymocytes, the production of IL-10, and T.sub.reg activity in splenic CD4.sup.+.sup.CD25.sup.+ .sup.T cells. This suppressive effect of T.sub.reg cells on T cell proliferation could be blocked by using anti-IL-10 neutralizing antibodies. In addition, CD4.sup.+.sup.CD25.sup.+.sup.CD44.sup.+ .sup.T.sub.reg cells expressed higher levels of IL-10 and were more potent in suppressing effector T cell proliferation than were CD4.sup.+.sup.CD25.sup.+.sup.CD44.sup.- .sup.cells. This study indicates the presence of two novel phenotypes of T.sub.reg cells in the thymus, the functional relevance of CD44 in defining T.sub.reg cell subsets, and the role of both IL-10 and Foxp3 in modulating the function of T.sub.reg cells.