To comprehensively characterize early CD4+ and CD8+ T cell responses to homocitrullinated peptides (HomoCitP) in a humanized mouse model of rheumatoid arthritis (RA).
Approach:
Mouse Model: Utilized humanized SE-expressing HLA-DRB1*04 transgenic (DR4tg) mice to study immune responses to HomoCitP.
Immunization: Mice were immunized with HomoCitJED peptide containing homocitrulline and a control peptide, LysJED.
Cell Analysis: Spleens and draining lymph nodes were harvested for single-cell suspensions and analyzed using flow cytometry.
Cytokine Detection: Proliferation and cytokine production were assessed in splenocytes and draining lymph node cells.
Key Findings:
CD4+ T cells from DR4tg mice proliferated in response to HomoCitP.
Increased production of pro-inflammatory cytokines was observed in response to HomoCitP.
Interpretation:
Homocitrullinated peptides can induce pro-inflammatory T cell activation.
Limitations:
The study focused on a specific mouse model and may not fully represent human RA.
Potential differences in immune responses between mice and humans were not addressed.
Conclusion:
This study provides insights into the cellular mechanisms through which homocitrullinated peptides may contribute to RA pathogenesis.
Combined rheumatoid factor and anticitrullinated protein antibody status appeared to modify the association between baseline rheumatoid arthritis disease activity and subsequent cardiovascular events in an international observational cohort.
