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Infection and Immunity, June 2000, p. 3269-3274, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Identification and Characterization of Murine
Cytotoxic T Cells That Kill Mycobacterium
tuberculosis
Celio L.
Silva1,* and
Douglas B.
Lowrie2
Department of Parasitology, Microbiology and
Immunology, School of Medicine of Ribeirão Preto, University
of São Paulo, Brazil,1 and
National Institute for Medical Research, London, United
Kingdom2
Received 27 October 1999/Returned for modification 13 December
1999/Accepted 14 March 2000
As 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
naïve 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
virulent Mycobacterium tuberculosis during 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.
*
Corresponding author. Mailing address: Department of
Parasitology, Microbiology and Immunology, School of Medicine of
Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil. Phone: 55 16 633 3035. Fax: 55 16 633 6631. E-mail: clsilva{at}beverly.fmrp.usp.br.
Infection and Immunity, June 2000, p. 3269-3274, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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