| First Author | Wang J | Year | 2010 |
| Journal | Mol Immunol | Volume | 48 |
| Issue | 1-3 | Pages | 137-46 |
| PubMed ID | 20869773 | Mgi Jnum | J:167093 |
| Mgi Id | MGI:4867146 | Doi | 10.1016/j.molimm.2010.08.017 |
| Citation | Wang J, et al. (2010) Neutralization of IL-4 reverses the nonresponsiveness of CD4+ T cells to regulatory T-cell induction in non-responder mouse strains. Mol Immunol 48(1-3):137-46 |
| abstractText | It is well established that naive cells can be converted by TGF-beta into CD4(+)CD25(+) regulatory T (Treg) cells with therapeutic potentials. Likewise, it is shown that all-trans retinoic acid (ATRA) can greatly enhance TGF-beta-induced Treg conversion, a phenomenon which has mainly been studied in C57BL/6 mice. Here we show that, although purified naive cells are highly susceptible to Treg generation, total CD4(+) T-cell populations from different mouse strains display significantly different sensitivities to TGF-beta/ATRA-induced Treg conversion. The resistance of 'non-responder' strains is associated with an enhanced production of IL-4 by memory T cells as well as an increased sensitivity of naive T cells to the action of IL-4. Importantly, neutralization of IL-4 overcomes the differences, thereby enabling TGF-beta/ATRA to generate large numbers of functional Treg cells from total CD4(+) T cells in a consistent manner across different mouse strains. Likewise, blockade of IL-4 significantly enhances TGF-beta/ATRA-induced Treg conversion from human naive T cells in the presence of memory cells. These results show that the inherent resistance of 'non-responder' mouse strains to Treg conversion induced by TGF-beta and ATRA can be reverted by neutralization of IL-4 and that inhibiting the action of IL-4 is beneficial or even necessary for consistent inducible Treg generation. |
