Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice

Both antigen-presenting cells and immune effector cells are required to eff ectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive "cross talk" between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of alpha/beta and gamma/delta T cells. Here we show that either cytokine is a ble to enhance survival of M. tuberculosis-infected BALB/c mice significant ly compared to application of IL-2. IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was ad ministered at the time of infection. Increased survival of M. tuberculosis- infected animals was observed following passive transfer of spleen cells ha rvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 fail ed to significantly impact on the number and composition of granulomas form ed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 to M. tuberculosis-treated animals resulted in a qualitatively diffe rent cellular immune response in spleen cells as reflected by increased tum or necrosis factor alpha and decreased gamma interferon secretion in respon se to M. tuberculosis-infected antigen-presenting cells.