Distinct regulatory roles of transforming growth factor-beta and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells

0333972 - ÚMG 2010 RIV GB eng J - Článek v odborném periodiku
Procházková, Jana - Frič, Jan - Pokorná, Kateřina - Neuwirth, Aleš - Krulová, Magdalena - Zajícová, Alena - Holáň, Vladimír
Distinct regulatory roles of transforming growth factor-beta and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells.
Immunology. Roč. 128, 1 Suppl (2009), e670-e678. ISSN 0019-2805. E-ISSN 1365-2567
Grant CEP: GA AV ČR KAN200520804; GA ČR GD310/08/H077; GA MŠMT 1M0506
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: alloantigen * cytokines * suppression
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.276, rok: 2009

The development and function of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are strictly regulated by cytokines. Here we show that TGF-b and IL-4 play a crucial and antagonistic role in the development of Tregs and have distinct effects on maintenance of natural (nTregs) and antigen-induced (iTregs) Tregs. We demonstrated that CD4+CD25+Foxp3+ iTregs develop upon alloantigenic stimulation in the presence of TGF-b exclusively from CD4+CD25-Foxp3- precursors. Both induction of Foxp3 expression and Treg proliferation were prevented when the cells were stimulated in the presence of IL-4. IL-4 decreased the number of Foxp3+ cells in a population of iTregs while it substantially supported the survival of nTregs. iTregs inhibit cell proliferation comparably to nTregs and their suppressive capacity is not modulated by IL-4. These data suggest that TGF-b and IL-4 differentially regulate the development and maintenance of Tregs but have no influence on the suppressive activity of Tregs.
Trvalý link: http://hdl.handle.net/11104/0178823