The contribution of CD8؉ T cells to the control of tuberculosis has been studied primarily during acute infection in mouse models. Memory or recall responses in tuberculosis are less well characterized, particularly with respect to the CD8 T-cell subset. In fact, there are published reports that CD8 ؉ T cells do not participate in the memory immune response to Mycobacterium tuberculosis. We examined the CD8 ؉ T-cell memory and local recall response to M. tuberculosis. To establish a memory immunity model, C57BL/6 mice were infected with M. tuberculosis, followed by treatment with anti-mycobacterial drugs and prolonged rest. ؉ and CD8 ؉ T cells in the lungs of immune mice expressed the activation marker CD69 and could be restimulated to produce gamma interferon (IFN-␥). In contrast, <6% of T cells in the lungs of naive challenged mice were CD69؉ at 1 week postchallenge, and IFN-␥ production was not observed at this time point. CD8؉ T cells from the lungs of both naive and memory mice after challenge were cytotoxic toward M. tuberculosis-infected macrophages. Our data indicate that memory and recall immunity to M. tuberculosis is comprised of both CD4؉ and CD8 ؉ T lymphocytes and that there is a rapid response of both subsets in the lungs following challenge.
Control of acute tuberculosis in mice involves participation of CD8ϩ T cells (6,22,37), although a recent publication argues for a more important role for this subset in control of persistent infection (38). Recent studies on the development and activation of mycobacterium-specific CD8 ϩ T cells have indicated that substantial numbers of activated CD8 ϩ T lymphocytes with both cytokine-secreting and cytotoxic functions are present in the lungs during the acute phase of infection in mice (13,19,(33)(34)(35). However, whether this acute response culminates in the development of memory CD8 ϩ T-cell populations that can respond robustly to a secondary Mycobacterium tuberculosis challenge is not clear. It is believed that a proper memory response develops after an infection is cleared. CD8 ϩ T cells play a prominent role during memory immune responses in intracellular bacterial infections with Listeria monocytogenes (11) and Chlamydia pneumoniae (31). In the mouse model and in humans, M. tuberculosis can be a persistent or latent infection. To study the memory response in this infection, it is useful to first reduce or eliminate the bacterial burden in the mouse tissues. It has been reported that the treatment of infected mice with antibiotics leads to the development of an immune response capable of reducing the bacterial burden after challenge (4). The major role in combating bacterial challenge during memory immune responses so far has been attributed exclusively to CD4 ϩ T cells (4). Earlier studies have argued against the participation of memory CD8 ϩ T cells in the recall immune responses in a murine model of tuberculosis (3,4,30). However, the development of a memory CD8 ϩ T-cell population during M. tuberculosis infection is supported by the findings that ...