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.
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Kasahara et al. (2021) studied this question.