| First Author | McKarns SC | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 4 | Pages | 2071-83 |
| PubMed ID | 15699137 | Mgi Jnum | J:96540 |
| Mgi Id | MGI:3530948 | Doi | 10.4049/jimmunol.174.4.2071 |
| Citation | McKarns SC, et al. (2005) Distinct effects of TGF-beta1 on CD4+ and CD8+ T cell survival, division, and IL-2 production: a role for T cell intrinsic Smad3. J Immunol 174(4):2071-83 |
| abstractText | TGF-beta1 is critical for maintaining T cell homeostasis. Smad3 has been implicated in this regulatory process, yet the cellular targets and molecular details remain poorly understood. In this study, we report that TGF-beta1 impairs the entry of CD4+ and CD8+ T cells into the cell cycle as well as their progression through subsequent rounds of division, and show that Smad3 is essential for TGF-beta1 to inhibit TCR-induced division of only CD4+ and not CD8+ T cells. Both CD8+ and CD4+ T cells from Smad3-/- mice were refractory to TGF-beta1-induced inhibition of IL-2 production, thus demonstrating that not all CD8+ T cell responses to TGF-beta1 are Smad3 independent. These TGF-beta1 effects were all T cell intrinsic, as they were reproduced in purified CD4+ and CD8+ T cells. Finally, we found that Smad3 was critical for the survival of CD8+, but not CD4+ T cells following activation ex vivo. The TCR-induced death of Smad3-/- CD8+ T cells was not dependent upon TNF-alpha production. Exogenous TGF-beta1 partially rescued the CD8+ T cells by signaling through a Smad3-independent pathway. TGF-beta1 also enhanced survival of TCR-stimulated CD4+CD44high T cells in a Smad3-independent manner. Collectively, these findings firmly establish for the first time that TGF-beta1 discriminately regulates CD4+ and CD8+ T cell expansion by signaling through distinct intracellular pathways. |
