LAUSR

HIV/SIV infection leads to a loss of CD4+ T-helper (Th) cells in number and function that begins during the acute phase and persists through the chronic phase of infection. In particular, there is a drastic decrease of Th17 and Th22 cells in the HIV/SIV-infected gastrointestinal (GI) tract as a source of Interleukin (IL)-17 and IL-22. These cytokines are vital in the immune response to extracellular pathogens and maintenance of the GI tract. However, innate lymphoid cells (ILCs) are a source of IL-17 and IL-22 during the early stages of an immune response in mucosal tissue and remain vital cytokine producers when the immune response is persistent. Here, we wanted to determine whether ILCs are a source of IL-17 and IL-22 in the SIV-infected colon and could compensate for the loss of Th17 and Th22 cells. As a control, we evaluated the frequency and number of ILCs expressing interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) We determined the frequency and number of cytokine-expressing ILC subsets and T-cell subsets within leukocytes from the colons of uninfected as well as acute and chronic SIV-infected colons without in vitro mitogenic stimulation. In the present study, we find that: 1) the frequency of IL-22, IFNγ, and TNFα, but not IL-17 producing ILCs are increased in the acutely infected colon and remain high during the chronically infected colon relative to cytokine expressing ILCs in the uninfected colon, 2) are a significant source of IL-22, IFNγ, and TNFα but not IL-17 when CD4+ T-lymphocytes in the gut lose their capacity to secrete these cytokines during SIV infection, and 3) the changes in the cytokines expressed by ILCs relative to CD4+ T-cells in the infected colon were not due to increases in the frequency or number of ILCs in relation to T-lymphocytes found in the tissue.