SELF-REACTIVE T-CELLS ARE ACTIVATED BY THE 65-KDA MYCOBACTERIAL HEAT-SHOCK PROTEIN IN NEONATALLY THYMECTOMIZED MICE

To elucidate the mechanism of autoimmune disease in neonatally thymectomized (NTX) mice, we have investigated the responsiveness of the self-reactive T cells which have not undergone clonal deletion in such animals. Consistent with a recent report (Yuuki et al., Eur. J. Immunol. 1990. 20: 1475), T cells bearing V-beta-11-gene products capable of recognizing I-E-encoded molecules were readily detected in the mature T cell pool of NTX BALB/c (I-E(d), Mls-2a) mice. The V-beta-11-bearing T cells in NTX mice expressed interleukin 2 receptors and responded normally to signals delivered through the T cell receptor. Notably, these T cells in NTX mice proliferated significantly after culture with the 65-kDa mycobacterial heat-shock protein, whose amino acid sequence is highly homoglous to that in eukaryotes. These results suggest that self-reactive T cells in NTX mice may be activated by heat-shock proteins derived from various pathogens and/or stressed autologous cells, resulting in the development of autoimmune diseases in such animals.