Immune responses in an untransfused patient with aplastic anemia: analysis of cytolytic and proliferative T cell clones.

Unexpected unidirectional reactivity was noted in MLC by the cells of an untransfused patient with aplastic anemia against cells from her genotypically HLA identical brother. To analyze this reactivity, lymphocytes from the patient were primed in vitro for six days with irradiated lymphocytes from the HLA identical brother and then cloned by limiting dilution in the presence of interleukin-2. Following a period of clonal expansion, the patient's cells were tested for specific proliferative (PLT) and cytolytic (CTL) activity against cells of the brother. Thirty-six clones demonstrated proliferative activity, 30 clones demonstrated cytolytic activity, and 114 clones showed neither. No clone demonstrated both cytotoxic and proliferative activity. Several patterns of specificity were seen for the cytolytic T cell (CTL) clones, including both allo- and autoreactivity. Two distinct patterns of specificity were noted for the proliferative clones: one reactive to cells from DR3-positive males; the other reactive only to cells from certain DR2-positive males and females. The DR3-restricted clones are presumably directed towards the H-Y minor histocompatibility antigen while the DR2-restricted clones are directed toward an undefined minor histocompatibility antigen. It is thus possible to isolate both alloreactive and autoreactive T cells from the peripheral blood of some untransfused patients with aplastic anemia.