Abstract
ABSTRACTAs we seek to develop and evaluate new vaccines against tuberculosis, it is desirable that we understand the mechanisms of protective immunity in our models. Adoptive transfer of protection with hsp65-specific T-cell clones from infected or vaccinated mice into naı̈ve mice had indicated that cytotoxic T cells can make a major contribution to protection. We characterized 28 CD4+CD8−and 28 CD4−CD8+hsp65-specific T-cell clones derived from infected or vaccinated mice. Half of the CD4+CD8−and 64% of the CD4−CD8+clones were cytotoxic. Cytotoxicity was associated with high expression of CD44 and gamma interferon production. Most (86%) of the cytotoxic CD4+CD8−clones lysed target cells via the Fas-FasL pathway, and most (83%) of the cytotoxic CD4−CD8+clones lysed target cells via cytotoxic granules. Only the clones using the granule-mediated pathway caused substantial loss of viability of virulentMycobacterium tuberculosisduring lysis of infected macrophages, and the degree of killing closely correlated with the availability of granule marker enzyme activity. Granule-mediated cytotoxicity thus may have a key role in protection against tuberculosis by delivering mycobactericidal granule contents.
References
25
Referenced
66
-
Bloom B. R. Fine P. E. M. The BCG experience: implications for future vaccines against tuberculosis Tuberculosis: pathogenesis protection and control. Bloom B. R. 1994 531 557 American Society for Microbiology Washington D.C.
(
10.1128/9781555818357.ch31
) 10.1128/IAI.66.1.169-175.1998
- Chan J. Kaufmann S. H. E. Immune mechanisms of protection Tuberculosis: pathogenesis protection and control. Bloom B. R. 1994 389 415 American Society for Microbiology Washington D.C.
10.1084/jem.175.4.1111
10.1084/jem.178.6.2243
10.1128/iai.65.4.1317-1320.1997
10.1002/eji.1830180110
10.1084/jem.178.6.2249
10.1016/S0171-2985(97)80085-X
10.1016/S1074-7613(00)80364-7
10.1128/iai.65.1.127-132.1997
- Lowrie D. B. Mononuclear phagocyte-mycobacterium interaction The biology of the mycobacteria Ratledge C. Stanford J. 2 1983 235 278 Academic Press London, United Kingdom / The biology of the mycobacteria / Mononuclear phagocyte-mycobacterium interaction by Lowrie D. B. (1983)
- Lowrie D. B. Colston M. J. Tascon R. E. Silva C. L. DNA encoding individual mycobacterial antigens protects mice against tuberculosis Vaccines 97: molecular approaches to the control of infectious diseases. Brown F. Burton D. Doherty P. Mekalanos J. Norrby E. 1997 163 166 Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y
10.1084/jem.180.4.1499
10.1046/j.1365-3083.1998.00419.x
10.1016/0882-4010(91)90054-E
-
Oddo M. Renno T. Attinger A. Bakker T. MacDonald H. R. Meylan P. R. A. Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis.J. Immunol.160199854485454
(
10.4049/jimmunol.160.11.5448
) / J. Immunol. / Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis by Oddo M. (1998) 10.1016/0923-2508(90)90029-P
10.1016/S0167-5699(97)80019-9
10.1016/0882-4010(92)90063-T
10.1128/iai.64.7.2400-2407.1996
10.1126/science.282.5386.121
10.1126/science.276.5319.1684
10.1111/j.1365-2249.1994.tb06544.x
10.1073/pnas.93.6.2588
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 27, 2002, 5:58 a.m.) |
Deposited | 2 years, 4 months ago (April 23, 2023, 11:02 a.m.) |
Indexed | 5 months ago (March 30, 2025, 3:23 p.m.) |
Issued | 25 years, 3 months ago (June 1, 2000) |
Published | 25 years, 3 months ago (June 1, 2000) |
Published Print | 25 years, 3 months ago (June 1, 2000) |
@article{Silva_2000, title={Identification and Characterization of Murine Cytotoxic T Cells That KillMycobacterium tuberculosis}, volume={68}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.68.6.3269-3274.2000}, DOI={10.1128/iai.68.6.3269-3274.2000}, number={6}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Silva, Celio L. and Lowrie, Douglas B.}, editor={Kaufmann, S. H. E.}, year={2000}, month=jun, pages={3269–3274} }