Differences between normal and autoimmune T cell responses to autologous erythrocytes and haemoglobin: Impairment of haptoglobin-mediated inhibition in NZB spleen cells

Helper T cells are required for development of the autoantibody responses to native mouse erythrocytes (MRBC) that spontaneously develop in NZB mice. However, the stimulus for these Th is not known. Therefore, we compared the abilities of splenic T cells from actively autoimmune old NZB mice and preautoimmune, young NZB mice with those of T cells from nonautoimmune strains of mice to respond to autologous erythrocytes. We found that autologous RBC ghosts, washed free of haemoglobin, induced low, but statistically significant, proliferative responses in T cells from old NZB mice but not in T cells from young NZB or from normal young and old BALB/c mice. In addition, autologous RBC lysates induced proliferative responses detectable by H-3-thymidine uptake in T cells from nonautoimmune as well as autoimmune mice. CD4(+) T cells accounted for most of the observed RBC lysate-induced proliferation, with virtually no response made by CD8(+) T cells or B cells. T cells from actively autoimmune NZB mice were not more active in their responses to RBC lysates than T cells from normal strains of mice in terms of their level of proliferation, kinetics, or dose response. Haemoglobin was the major stimulus in the autologous RBC lysates and a similar stimulation was seen with lysates and haemoglobins from horse, human, and mouse sources. Haptoglobin, a haemoglobin-binding serum protein, inhibited T cell responses to haemoglobin and haemoglobin-containing RBC lysates but did not have the same effect on these responses in T cells from either young or old NZB mice. Therefore, either or both of the RBC stimuli from autologous RBC might account for the helper T cell activity in autoimmune NZB mice. T cells in normal mice do not respond either to RBC lysates in the presence of haptoglobin or to RBC ghosts. (C) 1996 Academic Press Limited