Immunomodulatory potential of CD3+ CD4-CD8- double negative (DN) T cells in sooty mangabeys (105.7)

Abstract

Abstract Simian immunodeficiency virus (SIV) infection in natural hosts like sooty mangabeys (SM) is typically non-pathogenic and characterized by the absence of chronic immune activation. In contrast, SIV-infected Asian macaques, such as rhesus macaques (RM), progress to AIDS. CD3+ CD4-CD8- double negative (DN) T cells comprise <5% of circulating T cells in AIDS-susceptible species such as RM, but are present at significantly higher proportions (mean 20%) in SM. To investigate the significance of this difference, we compared the phenotype and function of DN T cells in SM and RM. γδ T cells, Tregs and NKT cells accounted for <15% of DN T cells in both SM and RM. SM DN T cells contained a significantly higher frequency of CXCR5-positive and CCR6-positive cells indicating ability to home to lymphoid tissue and mucosal sites of inflammation. Mitogen-stimulated DN T cells in both SM and RM were functionally similar to CD4+ T cells with regards to upregulation of CD40L and expression of Th1 (IFN-γ, IL-2), Th2 (IL-13) and Th17 (IL-17) cytokines. However, SM DN T cells produced significantly higher levels of IL-13 and IL-17, and contained significantly higher frequencies of Tregs compared to RM suggesting more potent immunomodulatory function. These data raise the possibility that the Treg and Th17 functionality of SM DN T cells are instrumental in regulating immune activation and gut mucosal integrity, features that help to prevent immunodeficiency in SIV-infected SM.