CLONALLY EXPANDED V(ALPHA)12-CELLS FROM A PATIENT WITH RHEUMATOID-ARTHRITIS ARE AUTOREACTIVE( (AV12S1),CD8+ T)

Objective. Previously, we showed that 15-20% of patients with rheumato id arthritis (RA) have oligoclonal expansions of peripheral blood CD8 T cells expressing T cell receptors encoded by the V(alpha)12 (AV12S1 ) gene. To better understand the significance of these expansions, the present study was undertaken to determine their specificity. Methods. We cloned and characterized V(alpha)12+,CD8+ T cells from the periphe ral blood of 1 RA patient with a clonal expansion of these T cells. Re sults. The T cell clones were autoreactive since they recognized autol ogous, but not allogeneic, antigen-presenting cells. Upon activation, these T cells secreted interleukin-4 and interleukin-10. The autoreact ive T cell clones were class I major histocompatibility complex (MHC) restricted, by either HLA-B60 or HLA-Cw3. Conclusion. A large populati on of class I MHC-restricted CD8+ T cells in a patient with RA is clon ally expanded and autoreactive. These cells define a novel immune aber ration in RA and provide a tool for defining the autoantigens that act ivate expanded T cell populations in vivo.