Early onset inhibition of lymphocytes in heterologous serum by high concentrations of concanavalin-A: Further studies of the role of complement with suramin and heated serum

Abstract

Activation of lymphocytes by concanavalin-A (Con-A) was assessed during a 6 h culture period (increased incorporation of [ 3H]uridine). Activation was enhanced to approximately the same extent by the trypanocidal agent suramin (300 μM) and by serum preheated at 53–56°C to inactivate complement. However, the combination of suramin and heated serum was inhibitory. Maximum enhancement occurred when suramin was added as late as an hour after the addition of Con-A. Reduced enhancement occurred when suramin was added at later times. The rate of loss of sensitivity to enhancement by suramin increased with increasing concentrations of Con-A. These results can be related to previous studies which suggest that a prior aggregation of surface receptor sites by Con-A is needed before components of the alternative complement pathway can bind and destroy lymphoid cells. Increasing the Con-A concentration would increase the number of cells which are susceptible to complement. Suramin would inactivate complement and prevent lymphocyte destruction. By analogy, in trypanosomiasis it is proposed that high concentrations of trypanosomal antigen cause an aggregation of the receptors of specific lymphocytes. This results in complement binding and lymphocyte destruction (immunological tolerance by clonal deletion). By inhibiting complement in vivo suramin would convert this tolerogenic response to an immunogenic response.