HEAT-SHOCK PROTEINS AND THE GAMMA-DELTA-T-CELL RESPONSE IN VIRUS-INFECTIONS - IMPLICATIONS FOR AUTOIMMUNITY

Macrophages expressing hsp65 mRNA+ and γδ TcR mRNA+ lymphocytes are found at high frequency late in the course of the pneumonia induced in mice by human influenza A viruses. The numbers of the two populations increase in parallel, after the time that infectious virus has been cleared from the lung. The range of TcR genes that are detected is consistent with, although not exclusive to, the pattern found by others for hybridoma cell lines that are reactive to hsp65. Secondary infection (in the absence of neutralizing antibody) greatly enhances both the rapidity and the magnitude of this γδ T cell response for mice that are primed with a different type A influenza virus, but not with an influenza B virus. This could be taken to indicate that the initial infection has induced the generation of influenza A virus-specific γδ T cell memory. However, when the primed σβ T cells are depleted from such mice by treatment with mAb to CD4 and CD8, the accumulation of both the hsp65 mRNA+ macrophages and the γδ TcR mRNA+ lymphocytes is greatly decreased. The results are consistent with the following hypothesis, which is highly speculative and based on limited data. The αβ T cell response that mediates virus clearance induces high levels of hsp65 expression in macrophages, which in turn stimulates the involvement of hsp65-reactive γδ T cells. Lymphokines/cytokines secreted by these γδ T cells then function to maintain macrophage activation, and to retain these macrophages in the respiratory tract after the time that the virus has been eliminated and the αβ T cells are no longer being stimulated. This serves to provide a nonspecific cover to protect the damaged lung from secondary bacterial infection during the process of tissue repair. If this model is correct, any virus-specific αβ T cell response is likely to promote a local hsp65+ macrophage/γδ T cell circuit. Although normally a protective mechanism, such interactions could potentially exacerbate autoreactivity if occurring in sites (e. g., the joint) where inflammatory cells may not be readily cleared by normal, physiological processes. © 1991 Springer-Verlag.