PROTECTION AGAINST TUBERCULOSIS BY BONE-MARROW CELLS EXPRESSING MYCOBACTERIAL HSP65

Although mice acquire only a slight degree of protection against tuber culosis by immunization with Mycobacterium leprae (M. leprae) hsp65 in incomplete Freund's adjuvant, protection is substantial following imm unization by injection with J774 macrophage-like tumour cells that exp ress the protein from the mycobacterial gene via a retroviral vector. We here took the same vector, used it to transfect the gene into norma l murine bone marrow cells in vitro, and then used the transfected cel ls to reconstitute haematopoiesis in lethally irradiated mice. Bone ma rrow-cell clonal expansion and production of the protein in vivo resul ted in specific delayed-type hypersensitivity and protection against c hallenge with Mycobacterium tuberculosis (M. tuberculosis) in about ha lf of recipients. Counts of live bacteria in liver at 3 weeks were fiv efold lower in delayed-type hypersensitivity (DTH)-positive than in DT H-negative mice. Other mice acquired neither DTH nor protection despit e the presence of the protein in peripheral blood.