Heterogeneity in phenotype and function of CD8+ and CD4/CD8 double-negative Natural Killer T cell subsets in sooty mangabeys

Background  We have recently reported the presence of CD8+ and CD4/8 double-negative (DN) natural killer T (NKT) lymphocytes in sooty mangabeys. To investigate differences in the two NKT cell subsets, we compared the phenotype and function of sooty mangabey CD8+ and DN NKT cells. Methods  Flow-sorted NKT lymphocytes from one SIV-negative sooty mangabey were subjected to limiting dilution cloning. Invariant NKT clones were characterized by flow cytometry and cytokine ELISA. Results  The majority of NKT clones displayed an effector memory phenotype and expressed CXCR3 and NKG2D. While CD8+ NKT subsets expressed significantly higher levels of granzyme B and perforin and produced more IFN-γ, the DN NKT subsets secreted significantly more IL-4, IL-13, and IL-10. Conclusions  The Th1 and Th2 cytokine bias of CD8+ and DN NKT cells, respectively, indicates the presence of functionally heterogeneous populations of NKT cells in sooty mangabeys.