CD8 Treg-Mediated Suppression of Naive CD4+ T Cell Differentiation into Follicular Helper T Cells

Background: The regulatory CD8(+) T (CD8(+) 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-FH) cells contribute by controlling the antibody production. In mice, CD8(+) Treg cells control the number and function of T-FH cells however the role of human CD8(+) Treg cells on the differentiation of naive CD4(+) T cells into T-FH cells has not been studied. Objectives: Here, we evaluated the ability of human CD183(+) CD8(+) Treg cells to suppress T-FH cell differentiation in vitro. Methods: Activated CD183(+)CCR7(+)CD45RA(-)CD8(+) Treg and CD183(+)CD25(high)ICOS(+)CD8(+) Treg cells were sorted and cocultured with naive CD4(+) T cells under T-FH differentiation condition. The differentiation of T-FH cells was evaluated by flow cytometry. Results: Our results showed that activated CD183(+)CD8(+) Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183(-)CD8(+) T cells. The CD183(+)CD25(high)ICOS(+)CD8(+) Treg cells suppressed T-FH cell differentiation and CD4(+) T cell proliferation in vitro which was not observed when CD183(+)CCR7(+)CD45RA(-)CD8(+) Treg were cocultured with naive CD4(+) T cells under T-FH cell differentiation condition. Conclusion: These results suggest that CD25(high)ICOS(+)CD183(+)CD8(+) Treg cells may regulate autoimmune and inflammatory responses mediated by T-FH cells.