PLoS Pathogens (May 2011)

A gamma interferon independent mechanism of CD4 T cell mediated control of M. tuberculosis infection in vivo.

  • Alena M Gallegos,
  • Jeroen W J van Heijst,
  • Miriam Samstein,
  • Xiaodi Su,
  • Eric G Pamer,
  • Michael S Glickman

DOI
https://doi.org/10.1371/journal.ppat.1002052
Journal volume & issue
Vol. 7, no. 5
p. e1002052

Abstract

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CD4 T cell deficiency or defective IFNγ signaling render humans and mice highly susceptible to Mycobacterium tuberculosis (Mtb) infection. The prevailing model is that Th1 CD4 T cells produce IFNγ to activate bactericidal effector mechanisms of infected macrophages. Here we test this model by directly interrogating the effector functions of Th1 CD4 T cells required to control Mtb in vivo. While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFNγ or TNF and does not require the perforin or FAS effector pathways. Adoptive transfer of Th17 CD4 T cells specific for ESAT-6 partially inhibited Mtb growth while Th2 CD4 T cells were largely ineffective. These results imply a previously unrecognized IFNγ/TNF independent pathway that efficiently controls Mtb and suggest that optimization of this alternative effector function may provide new therapeutic avenues to combat Mtb through vaccination.