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

Abstract

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 (TFH) cells contribute by controlling the antibody production. In mice, CD8+ Treg cells control the number and function of TFH cells however the role of human CD8+ Treg cells on the differentiation of naive CD4+ T cells into TFH cells has not been studied. Objectives: Here, we evaluated the ability of human CD183+ CD8+ Treg cells to suppress TFH cell differentiation in vitro. Methods: Activated CD183+CCR7+CD45RA−CD8+ Treg and CD183+CD25highICOS+CD8+ Treg cells were sorted and cocultured with naïve CD4+ T cells under TFH differentiation condition. The differentiation of TFH 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+CD25highICOS+CD8+ Treg cells suppressed TFH cell differentiation and CD4+ T cell proliferation in vitro which was not observed when CD183+CCR7+CD45RA−CD8+ Treg were cocultured with naïve CD4+ T cells under TFH cell differentiation condition. Conclusion: These results suggest that CD25highICOS+CD183+CD8+ Treg cells may regulate autoimmune and inflammatory responses mediated by TFH cells.