MAIT cells, iNKT cells, and γδT cells respond to non-peptide antigens and exhibit a poised state at baseline, enabling rapid activation of cytokine production and cytotoxic activity upon stimulation. However, the role(s) innate-like lymphocytes may play in autoimmune diseases are not well understood. We assessed the frequencies and properties of innate-like lymphocytes in patients with seropositive rheumatoid arthritis (RA) and several other types of autoimmune arthritis (seronegative RA, juvenile idiopathic arthritis, and spondyloarthritis). Interestingly, the frequency of MAIT cells is sharply reduced in the blood of patients with seropositive rheumatoid arthritis, similar to published observations in chronic infections such as tuberculosis and hepatitis C virus. Importantly, MAIT cells are not enriched in synovial fluid aspirated from actively inflamed joints. Nonetheless, MAIT cells in synovial fluid are activated, as evidenced by expression of HLA-DR and PD-1, and they produce IFNγ, TNF, and IL-17A upon stimulation. We hypothesized that MAIT cell numbers might be low due to increased cell death. Indeed, MAIT cells have higher levels of activated caspases than other T cell subsets, and their numbers drop drastically when cultured in the presence or absence of CD3- and CD28-mediated stimulation, despite proliferation at nearly the same rate as CD4 and CD8 T cells. The mechanism of this process is not yet clear, but we suspect that it may explain the low frequency of MAIT cells in patients with RA. Additional studies are in progress to further characterize MAIT cells in RA, including mechanisms that may result in MAIT cell depletion in RA.