CD8 Treg-Mediated Suppression of Naive CD4+ T Cell Differentiation into Follicular Helper T Cells
<b><i>Background:</i></b> The regulatory CD8<sup>+</sup> T (CD8<sup>+</sup> Treg) cells play an important role in immune tolerance and have been implicated in several human autoimmune diseases. In this context, follicular helper T (T<sub>FH</sub>) cells contribute by controlling the antibody production. In mice, CD8<sup>+</sup> Treg cells control the number and function of T<sub>FH</sub> cells however the role of human CD8<sup>+</sup> Treg cells on the differentiation of naive CD4<sup>+</sup> T cells into T<sub>FH</sub> cells has not been studied. <b><i>Objectives:</i></b> Here, we evaluated the ability of human CD183<sup>+</sup> CD8<sup>+</sup> Treg cells to suppress T<sub>FH</sub> cell differentiation in vitro. <b><i>Methods:</i></b> Activated CD183<sup>+</sup>CCR7<sup>+</sup>CD45RA<sup>−</sup>CD8<sup>+</sup> Treg and CD183<sup>+</sup>CD25<sup>high</sup>ICOS<sup>+</sup>CD8<sup>+</sup> Treg cells were sorted and cocultured with naïve CD4<sup>+</sup> T cells under T<sub>FH</sub> differentiation condition. The differentiation of T<sub>FH</sub> cells was evaluated by flow cytometry. <b><i>Results:</i></b> Our results showed that activated CD183<sup>+</sup>CD8<sup>+</sup> Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183<sup>−</sup>CD8<sup>+</sup> T cells. The CD183<sup>+</sup>CD25<sup>high</sup>ICOS<sup>+</sup>CD8<sup>+</sup> Treg cells suppressed T<sub>FH</sub> cell differentiation and CD4<sup>+</sup> T cell proliferation in vitro which was not observed when CD183<sup>+</sup>CCR7<sup>+</sup>CD45RA<sup>−</sup>CD8<sup>+</sup> Treg were cocultured with naïve CD4<sup>+</sup> T cells under T<sub>FH</sub> cell differentiation condition. <b><i>Conclusion:</i></b> These results suggest that CD25<sup>high</sup>ICOS<sup>+</sup>CD183<sup>+</sup>CD8<sup>+</sup> Treg cells may regulate autoimmune and inflammatory responses mediated by T<sub>FH</sub> cells.