CYTOKINE SECRETION BY CD4 T-LYMPHOCYTES ACQUIRED IN RESPONSE TO MYCOBACTERIUM-TUBERCULOSIS INFECTION

The results of this study in which CD4 T cells were harvested from mice at various times during the course of a virulent Mycobacterium tuberculosis infection and examined for their secretion of cytokines during culture in vitro with bone marrow-derived macrophages presenting mycobacterial Ag, provide evidence for the existence of two separate waves of cytokine-producing CD4 cells. The first, which peaks at the time at which protective immunity was maximally expressed, was characterized as a IFN-gamma-secreting cell population that preferentially recognized macrophages presenting mycobacterial culture filtrate proteins, or that were infected with the live organism. A second population, which emerged 20 to 40 days later at a time when the infection had been contained, secreted IL-4 in response to the filtrate proteins, but also reacted particularly strongly to the 65-kDa (hsp60) heat shock protein molecule of M. tuberculosis. These data indicate that acquired immunity to tuberculosis infection involves the production of both Th1- and Th2-like cell populations that differ in terms of their kinetics of emergence and loss, and in terms of their Ag specificity.