Immunotherapeutics for tuberculosis in experimental animals: is there a common pathway activated by effective protocols?
The increasing threat posed by drug-resistant strains of M. tuberculosis is leading to a reappraisal of the possibility of treating tuberculosis (TB) by immunotherapy. We analyze 6 strategies that have been shown to be therapeutic in animal models of TB and identify a common pathway underlying the activity of the superficially different immunotherapeutic protocols. This pathway involves enhanced induction of CD8(+) cytotoxic T lymphocytes (CTLs) and down-regulation of interleukin-4 and transforming growth factor- beta , leading to further enhancement of the activity of CD8(+) CTLs and of other microbicidal pathways. This unifying analysis strengthens the rationale for future trials of immunotherapy in humans and points to surrogate markers that could be studied in such trials.
Rook
Graham A W
GA
Centre for Infectious Diseases and International Health, University College London, London W1T 4JF, UK. g.rook@ucl.ac.uk
Lowrie
Douglas B
DB
Hernàndez-Pando
Rogelio
R
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000628:therapy; D032581:Tuberculosis Vaccines / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D032581:Tuberculosis Vaccines; D015847:Interleukin-4