| First Author | McCarron MJ | Year | 2014 |
| Journal | J Clin Invest | Volume | 124 |
| Issue | 10 | Pages | 4375-86 |
| PubMed ID | 25157822 | Mgi Jnum | J:217644 |
| Mgi Id | MGI:5615081 | Doi | 10.1172/JCI76179 |
| Citation | McCarron MJ, et al. (2014) TGF-beta prevents T follicular helper cell accumulation and B cell autoreactivity. J Clin Invest 124(10):4375-86 |
| abstractText | T follicular helper (Tfh) cells contribute to the establishment of humoral immunity by controlling the delivery of helper signals to activated B cells; however, Tfh development must be restrained, as aberrant accumulation of these cells is associated with positive selection of self-reactive germinal center B cells and autoimmunity in both humans and mice. Here, we show that TGF-beta signaling in T cells prevented Tfh cell accumulation, self-reactive B cell activation, and autoantibody production. Using mice with either T cell-specific loss or constitutive activation of TGF-beta signaling, we demonstrated that TGF-beta signaling is required for the thymic maturation of CD44(+)CD122(+)Ly49(+)CD8(+) regulatory T cells (Tregs), which induce Tfh apoptosis and thus regulate this cell population. Moreover, peripheral Tfh cells escaping TGF-beta control were resistant to apoptosis, exhibited high levels of the antiapoptotic protein BCL2, and remained refractory to regulation by CD8+ Tregs. The unrestrained accumulation of Tfh cells in the absence of TGF-beta was dependent on T cell receptor engagement and required B cells. Together, these data indicate that TGF-beta signaling restrains Tfh cell accumulation and B cell-associated autoimmunity and thereby controls self-tolerance. |
