T-HELPER-1 DOMINATED RESPONSES TO ERYTHROCYTE BAND-3 IN NZB MICE

Band 3, the red blood cell (RBC) anion channel protein, is the target autoantigen for the pathogenic RBC autoantibodies and T-helper (Th) ce lls in New Zealand Black (NZB) mice with autoimmune haemolytic anaemia (AIHA). To determine the subpopulation of these Th cells, they were s timulated with Band 3 and the profile of the cytokines elaborated by t he responding cells was measured. NZB T cells stimulated with Band 3 p roduced high levels of the Th1 cytokine, interferon-gamma (IFN-gamma), but little or no interleukin-4 (IL-4), IL-5 or IL-10. Similar pattern s were produced by NZB T cells responding to a spectrin preparation fr om the RBC membrane skeleton, or to mycobacterial heat-shock protein ( hsp) 65 following immunization of mice with hsp 65 in incomplete adjuv ant. By contrast, T cells from CBA mice similarly immunized with hsp 6 5 produced high levels of IL-4 and IL-5 in response to hsp 65. Examina tion of the isotype of the RBC-bound immunoglobulins in NZB mice revea led that immunoglobulin G2a (IgG2a) autoantibodies were the first to b e detected in most mice and that later in the disease, IgG3 autoantibo dies were often prominent. It is concluded that, contrary to expectati on, the development of RBC autoantibodies in NZB mice is associated wi th Th1 cytokine-dominated responses.