Citrullinated proteins, derived from the conversion of peptidyl-arginine to peptidyl-citrulline, are present in the joints of rheumatoid arthritis (RA) patients who also produce high levels of anti-citrullinated protein antibodies (ACPAs). T cells also have a role in RA and are thought to be involved in initiating, controlling and driving antigen-specific immune responses. We and others found that mice immunized with human fibrinogen (HF) or human citrullinated fibrinogen (HCF) develop mild inflammatory arthritis and peripheral T cells proliferate in response to HCF and HF. To determine if HCF-reactive T cells contribute to disease, DBA1/J mice were immunized with HCF and at various time points, T cells were assessed directly ex vivo or cultured in vitro. T cells were evaluated ex vivo for the presence of activation markers and cytokine production after antigen stimulation; T cell lines were cultured in vitro with antigen and IL-2 and evaluated in the same manner. Following two immunizations, mice produced CD4 T cells with an activated phenotype (CD44hi+CD62L-); TNFα and IL-17 were produced by CD4 T cells in response to HCF. T cell lines produced high levels of TNFα, IL-17, and IL-6 when stimulated by HCF, and one line also produced IFNγ. In sum, CD4 T cells are activated during disease progression and exhibit an inflammatory phenotype that may be pathogenic. T cell lines are being evaluated in vivo to determine if they can precipitate or accelerate disease.
- Copyright © 2011 by The American Association of Immunologists, Inc.