PREVENTION OF AUTOIMMUNE LYSIS BY T-CELLS WITH SPECIFICITY FOR A HEAT-SHOCK PROTEIN BY ANTISENSE OLIGONUCLEOTIDE TREATMENT

T lymphocytes with specificity for the bacterial heat shock protein (h sp) 60 recognize stressed host cells, thus possibly promoting pathogen esis of certain infectious and autoimmune diseases. Here, we show that autoimmune destruction of stressed Schwann cells and macrophages by c ytotoxic T lymphocytes raised against mycobacterial hsp60 can be inhib ited by the use of hsp60-specific antisense oligodeoxynucleotides (A-O DNs). The inhibitory effect of hsp60 A-ODNs was specific because lysis of murine cytomegalovirus-infected host cells by virus-specific cytot oxic lymphocytes was not affected. Immunoblot analysis and immunopreci pitation studies suggest that different forms of stress increase hsp60 synthesis in Schwann cells and that this neosynthesis is reduced by h sp60 A-ODNs. These findings (i) provide evidence for participation of endogenous hsp60 in the recognition of stressed host cells by mycobact erial hsp60-crossreactive T cells and (ii) suggest the feasibility of inhibiting autoimmune reactions by target-cell treatment with specific A-ODNs.