2013. fluid of SIV-infected RMs. These numerical changes were coupled with improved proliferation and a highly general public T cell receptor alpha (TCR) repertoire in the MAIT cell compartment without redistribution to additional anatomical sites. Collectively, our data display systemically decreased frequencies of MAIT cells likely attributable to enhanced turnover in SIV-infected RMs. This process may impair protecting immunity against particular opportunistic infections with progression to AIDS. IMPORTANCE The data presented with this study reveal for the first time that MAIT cells are systemically depleted in an AIDS virus illness. These findings provide a fresh mechanistic link with our current understanding of HIV/SIV pathogenesis and implicate MAIT cell depletion in the disease process. Intro Mucosa-associated invariant T (MAIT) cells are relatively abundant in humans, comprising 1 to 10% of peripheral blood T cells (1,C3) and up to 45% of liver lymphocytes (4, 5). Lower Rabbit Polyclonal to CROT frequencies are present in the gastrointestinal (GI) tract, lung, and mesenteric lymph nodes (MLNs) (2, 6). Classically defined by the manifestation of Benzo[a]pyrene a semi-invariant TRAV1-2/TRAJ33 (V7.2/J33) T cell receptor alpha (TCR) chain (7), MAIT cells recognize microbial vitamin B2 metabolites presented in association with the major histocompatibility complex class I-related molecule MR1 (8,C12). These conserved features bestow common reactivity against an array of bacterial and fungal varieties (13, 14), permitting MAIT cells to act as innate-like antimicrobial guardians at mucosal sites via the secretion of proinflammatory and tissue-protective cytokines, such as interleukin 17 (IL-17), tumor necrosis element (TNF), and gamma interferon (IFN-) (2, 9). The large quantity of MAIT cells in peripheral blood and mucosal cells, combined with their broad reactivity and practical properties, suggests a key role in main immune defense and various pathological claims (2, 9). Indeed, multiple reports possess described a loss of circulating MAIT cells in diseases with an inflammatory component, such as obesity and type II diabetes (15), inflammatory bowel disease (16), tuberculosis (2, 17), and human being immunodeficiency computer virus (HIV) disease (18,C20). MAIT cells also look like highly triggered under these conditions and may become recruited to cells sites of swelling (15, 16, 19). Although MAIT cells are neither directly activated nor directly infected by HIV (20), earlier studies have consistently shown selective depletion of this subset in the peripheral blood of HIV-infected individuals and simian immunodeficiency computer virus (SIV)-infected Asian macaques Benzo[a]pyrene (18,C20). However, the underlying mechanisms remain unclear. It is founded that CD4+ T cells are lost in the GI tract during HIV/SIV illness (21, 22). Moreover, epithelial integrity is definitely compromised from the connected immunopathology, leading to microbial translocation and systemic immune activation (23, 24). This process could feasibly travel MAIT cell activation, cytokine secretion, and potential migration to sites of swelling and/or bacterial/fungal infiltration. In this study, we conducted a comprehensive analysis of MAIT cell populations across multiple anatomical sites in healthy and SIV-infected rhesus macaques (RMs). Our data reveal a systemic loss of MAIT cells likely attributable to improved turnover in the establishing of SIV illness. These findings provide a mechanistic link with our current understanding of HIV/SIV pathogenesis and implicate MAIT cell depletion in the disease process. MATERIALS AND METHODS Animals. The study cohort comprised 29 SIV-infected RMs (10 chronically infected with SIVsmE660, 5 chronically infected with SIVsmE543, 8 chronically infected with SIVmac239, and 6 with SIVmac239-connected simian AIDS [sAIDS]) and 25 SIV-uninfected RMs (Table 1). Peripheral blood mononuclear cells (PBMCs) Benzo[a]pyrene were isolated by standard denseness gradient centrifugation. Bronchoalveolar lavage (BAL) fluid samples were filtered, centrifuged.