Clonally expanded Valpha12+ (AV12S1),CD8+ T cells from a patient with rheumatoid arthritis are autoreactive.
OBJECTIVE
Previously, we showed that 15-20% of patients with rheumatoid 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 peripheral blood of 1 RA patient with a clonal expansion of these T cells.


RESULTS
The T cell clones were autoreactive since they recognized autologous, but not allogeneic, antigen-presenting cells. Upon activation, these T cells secreted interleukin-4 and interleukin-10. The autoreactive T cell clones were class I major histocompatibility complex (MHC) restricted, by either HLA-B60 or HLA-Cw3.


CONCLUSIONS
A large population of class I MHC-restricted CD8+ T cells in a patient with RA is clonally expanded and autoreactive. These cells define a novel immune aberration in RA and provide a tool for defining the autoantigens that activate expanded T cell populations in vivo.
Behar
S M
SM
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Roy
C
C
Lederer
J
J
Fraser
P
P
Brenner
M B
MB
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000032:analysis; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D015847:Interleukin-4