PROLIFERATIVE RESPONSES OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM NORMAL DOGS AND DOGS WITH AUTOIMMUNE HEMOLYTIC-ANEMIA TO RED-BLOOD-CELL ANTIGENS

Autoimmune haemolytic anaemia (AIHA), one of the most common autoimmun e diseases of the dog, is characterised by binding of autoantibody to erythrocyte membrane antigens leading to a decreased red blood cell (R BC) life-span. Failure of self-tolerance with activation of autoreacti ve T-lymphocytes is thought to play a key role in the initiation of su ch autoimmune events. Peripheral blood mononuclear cells (PBMC) were o btained from 11 clinically normal dogs, six clinically normal relative s of two littermate dogs which died from AIHA, and four dogs which had recovered from primary AIHA. Cells were stimulated in vitro with a pa nel of canine RBC-derived antigens (RBC membranes, glycophorin, spectr in, five 15-mer glycophorin peptides), the non-recall antigen keyhole limpet haemocyanin (KLH), and the mitogen concanavalin A (Con A). The kinetics of the proliferative responses to specific antigens were asse ssed by serially sampling the cultures from days 4 to 10. PBMC from al l dogs responded strongly to Con A (day 2) and to KLH (maximal respons e on days 7 to 10) under appropriate culture conditions. Two of 11 nor mal dogs responded weakly to RBC membranes (mean stimulation index = 4 .25). In contrast, PBMC from all dogs recovered from AIHA responded to RBC membranes (mean SI=9.2+/-2.5) and occasionally to other erythrocy te antigens. Similar responses were recorded with PBMC from dogs relat ed to AIHA cases. It is considered that although normal individuals ha rbour erythrocyte-reactive lymphocytes, such cells are primed in dogs with AIHA or a genetic susceptibility to this disease. (C) 1997 Elsevi er Science B.V.