Investigation of cytotoxic CD4+ T cells in systemic lupus erythematosus 3565

Description Cytotoxic CD4+ T cells (CD4-CTLs) represent a subset of CD4+ T cells that, rather than performing “helper” functions, are capable of targeting and killing cells in an MHC-II-restricted fashion. While they account for only ∼2% of circulating CD4+ T cells under normal conditions, the prevalence of CD4-CTLs expands in many contexts, playing protective roles in anti-viral and anti-tumor responses, while promoting pathogenesis of autoimmune diseases. In Systemic Lupus Erythematosus (SLE), CD4-CTLs expand in patients with moderate to severe disease and are implicated in both promoting an inflammatory environment and suppressing regulatory T cells. The goal of this work is to better understand the role and origin of CD4-CTLs in SLE. Surprisingly, screening of CD4-CTL populations from individuals with low or unknown SLE Disease Activity Index (SLEDAI) scores versus Healthy Controls (HC) revealed no significant change in the frequency of CD4-CTL populations. Screening of individuals with moderate SLEDAI scores, however, revealed a significant increase in CD4-CTL populations, in agreement with previously published studies. For both HC and SLE groups, polarization of CD4+ T cells toward a CD4-CTL phenotype and induction of target cell killing was accomplished most effectively through combined treatment with IL-15 and anti-CD3. This work suggests that CD4-CTL populations positively correlate with SLEDAI scores and that the pathway for polarization of CD4-CTLs in SLE is intact.