Limited heterogeneity of T cell receptor BV usage in aplastic anemia

Immune mediation of aplastic anemia (AA) has been inferred from clinical re sponsiveness to immunosuppressive therapies and a large body of circumstant ial laboratory evidence. However, neither the immune response nor the natur e of the antigens recognized has been well characterized. We established a large number of CD4 and CD8 T cell clones from a patient with AA and analyz ed their T cell receptor (TCR) usage. Most CD4 clones displayed BV5, wherea s most CD8 clones displayed BV13. We found sequence identity for complement arity determining region 3 (CDR3) among a majority of CD4 clones; the same sequence was present in marrow lymphocytes from four other patients with AA but was not detected in controls. The dominant CD4 clone showed a Th1 secr etion pattern, lysed autologous CD34 cells, and inhibited their hematopoiet ic colony formation. In three of four patients, successful immunosuppressiv e treatment led to marked decrease in clones beating the dominant CDR3 BV5 sequence. These results suggest surprisingly limited heterogeneity of the T cell repertoire in an individual patient and similarity at the molecular l evel of the likely pathological lymphocyte response among multiple patients with AA, consistent with recognition of limited numbers of antigens shared by individuals with the same HLA type in this disease.