THE MYCOBACTERIUM-TUBERCULOSIS 71-KDA HEAT-SHOCK PROTEIN INDUCES PROLIFERATION AND CYTOKINE SECRETION BY MURINE GUT INTRAEPITHELIAL LYMPHOCYTES

Murine intraepithelial lymphocytes (IEL) respond poorly to T cell mito gens and to monoclonal antibody stimulation of T cell receptor (TCR)- and CD3- associated molecules. In contrast, we found that a soluble ex tract of Mycobacterium tuberculosis (Mtb), but not purified protein de rivative of tuberculin, induced significant proliferative responses in IEL cultures.The active component was apparently a heat shock protein (HSP), since recombinant 7 1-kDa HSP f rom Mtb induced IEL to prolife rate, while 65-kDa HSP from M. bovis and M. leprae did not. Both alpha /beta and gamma/delta TCR-enriched IEL gave proliferative responses to 71-kDa HSP. Further, culture supernatants from IEL stimulated with 71 -kDa HSP contained elevated levels of interleukin-(IL)-3/granulocyte-m acrophage colony-stimulating factor, interferon-gamma and IL-6, but no t IL-2, IL-4, IL-5 or transforming growth factor-beta. Finally, severa l IEL T cell clones have been maintained for up to 6 weeks, when stimu lated with 71-kDa HSP, IL-2 and feeder cells. Our results show that th e 71-kDa HSP of Mtb induces IELT cells to divide and to secrete cytoki nes and this may offer a model for cloning and study of IEL T cells in vitro.