T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis

Abstract

We sought to protect CBA mice against tuberculosis using in vivo transfer of a T-cell line previously shown to be capable of I-A-restricted recognition of peritoneal macrophages infected in vitro with Mycobacterium tuberculosis. This line induces total bacteriostasis in vitro. In mice that received 500 rads of irradiation 48 h before infection, the T-cell line caused significant prolongation of life when given intravenously with a challenge dose of 5 x 106 organisms. Similar experiments with two other T-cell lines showed that these lines offered no protection. Bacterial load at the time of death was inversely related to the time of survival. Thus, death occurred at a lower bacterial load in adoptively protected mice, implying the contribution of an immunopathological component in these animals. The protective T-cell line, which was CD4+ CD8-, had no effect on the rate of growth of strain BCG in CBA nulnu mice or M. tuberculosis in fully T-cell-deprived mice. This could indicate that CD8+ cells play a role in this system or that there is a need for the recruitment of interleukin 2-producing cells in the recipient. Experiments with monoclonal antibodies to selectively deplete T-cell subsets in normal CBA mice showed that depletion of CD4+ cells strikingly shortened survival, whereas depletion of CD8+ cells did not. However, CD8-depleted mice died with a lower bacterial load than those found in nondepleted

Changes in T‐Lymphocyte Subsets in Lungs and Spleens of Mice with Slowly Progressive Primary Mycobacterium tuberculosis Infection: Involvement of Unconventional T‐Cell Subsets

“…Both CD4 þ and CD8 þ cells are involved in controlling bacillary growth through the production of IFN-␥ and cytolysis of infected macrophages [2,[23][24][25][26]. Although both phenotypes possess cytolytic activity, CD8 þ cells may have a broader target spectrum [27].…”

Cancer Prevention by Adoptive Transfer of Antigen 60‐Activated Immunocompetent Cells

“…The purity of Tlymphocyte and macrophage preparations used in adoptive transfer trials were controlled prior to use by various methods, notably by using specific antibodies. Mice were subjected to whole body -irradiation (500 rads, 7.81 min, 60 cm, 64 rads/ min, 250 KV) in a 60 Co gamma-emitter (Atomic Energy of Canada), 24 h before adoptive transfer [17] of intraperitoneally injected 8 2 10 6 macrophages/200 l buffer and/or intravenously injected 8 2 10 7 T lymphocytes (from the spleen or lymph nodes) / 200 l buffer. Controls included adoptive transfers of non-activated lymphocytes, with or without non-activated macrophages, and of macrophages.…”

The Regulation of Pulmonary Immunity

“…A role for CMI was demonstrated for protection against Mtb infection (Suter, 1961;Leveton et al, 1989). In a guinea pig model, it was demonstrated that in animals given a low dose of Mtb, the organisms replicated in a log phase until Days 19 or 20, after which exponential growth ceased .…”