Characterization of the SARS-CoV-2-Specific T Cell Responses in Rheumatoid Arthritis Subjects Vaccinated for COVID-19 Protection.

The efficacy of mRNA-based vaccines to prevent COVID-19 in autoimmune patients is controversial due to immunosuppressive therapies. Here, we characterized the T cell responses to SARS-CoV-2 in rheumatoid arthritis (RA) subjects, who received as few as one or up to seven vaccine injections. The study population had different disease severities and an association with other autoimmune comorbidities. All the subjects studied showed SARS-CoV-2 spike-specific CD4+ T helper (Th) cells in circulation, and in most of the subjects, CD8+ cytotoxic T cells. CD4+ and CD8+ T cells were CCR6+, suggesting trafficking to tissues. T cell memory did not correlate with the number of vaccine boosts received. Nonspike-specific T cells were enumerated in subjects who had symptomatic or asymptomatic COVID-19. Spike- and nonspike-specific regulatory T cells (Treg) were detectable in most subjects. CD4- CD8- double-negative (DN) T cells expanded in response to SARS-CoV-2 peptides. DN T cells co-cultured with autologous myeloid dendritic cells (DC) differentiated into CD8+ T cells, depending upon the strength of the stimuli. RA subjects responded to mRNA-based vaccination for COVID-19 protection, with no correlation with the number of injections. DN T cells differentiated into CD8+ T cells after stimulation, potentially exacerbating inflammation in RA vaccine recipients.