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

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. © 2011 gallegos et al.