Role of NKG2a/c⁺CD8⁺ T cells in pathogenic versus non-pathogenic SIV infections

Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in the blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2_a/c ⁺CD8⁺ T cells increase in the blood and intestine of AGM in response to SIVagm infection in contrast to SIVmac infection in macaques, the latter modeling HIV infection. NKG2_a/c ⁺CD8⁺ T cells were not expanded in lymph nodes, and CXCR5⁺NKG2_a/c ⁺CD8⁺ T cell frequencies further decreased after SIV infection. Genome-wide transcriptome analysis of NKG2_a/c ⁺CD8⁺ T cells from AGM revealed the expression of NK cell receptors, and of molecules with cytotoxic effector, gut homing, and immunoregulatory and gut barrier function, including CD73. NKG2_a/c ⁺CD8⁺ T cells correlated negatively with IL-23 in the intestine during SIVmac infection. The data suggest a potential regulatory role of NKG2_a/c ⁺CD8⁺ T cells in intestinal inflammation during SIV/HIV infections.