Year: 2025
Type: article
Abstract: 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. Topic Categories Basic Autoimmunity (BA)
Source: The Journal of Immunology
Institution: Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416449028
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