T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis.
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 10(6) 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 nu/nu 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 controls, and the lesions in CD8-depleted mice were histopathologically distinct. These results suggest that the CD8+ cells either down-regulate bacteriostasis or cause immunopathology in this model and that it is the CD4+ cells that are the major protective subset in long-term protection experiments.
Leveton
C
C
Department of Medical Microbiology, University College, London, United Kingdom.
Barnass
S
S
Champion
B
B
Lucas
S
S
De Souza
B
B
Nicol
M
M
Banerjee
D
D
Rook
G
G
D000818:Animals; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008168:Lung / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D009929:Organ Size; D010641:Phenotype; D013154:Spleen; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000637:transplantation*; D014376:Tuberculosis / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D014774:Virulence