Functional characterization of clonal cd4 populations in rheumatoid arthritis (ra)

Clonal expansion of CD4 T cells in the peripheral blood compartment is a characteristic finding in RA patients and is only infrequently found in patients with psoriatic arthritis and healthy controls. To address the question whether the expanded clonotypes have unique functional properties, which may explain the preferential in vivo expansion in RA, we have isolated such T cell clones from 5 patients. In vivo expanded CD4 T ceils were autoreactive to ubiquitously distributed autoantigens. All of these T cell clones lacked the expression of the CD28 and CD7 cell surface marker molecules. To confirm this phenotype, PBMC from an additional 10 patients were purified and the appropriate T cell subsets were analyzed for clonal expansion. All in vivo expanded clonotypes expressed the CD4+ CD28" CD7" phenotype. Co-stimulation mediated by the CD28 molecule has been shown to be pivotal for the activation of CD4+ T cells. To analyze whether the in vivo expanded T cells are independent of costimulatory molecules, we have examined the response of CD4 CD28" T cell clones to anti-CD3 cross-linking in the presence and absence of co-stimulatory signals. CD4+ CD28" T cells were dependent upon co-stimulatory signals, distinct from the traditional CD28/CTLA-4-CD80/CD86 interaction, for optimal induction of proliferative responses, CD25 expression and for the prevention of anergy. The production of lymphokines was independent of co-stimulatory signals. These data suggest that, in RA patients, selected CD4 CD7' CD28" T cells utilize a unique co-stimulatory pathway which may facilitate these cells to escape peripheral tolerance and to proliferate in vivo.