(i) Evidence for exaggerated expression of cytokines that counterbalance Treg function
It is well recognized that proinflammatory cytokines can suppress the generation and function of Treg cells. By directly comparing the transcriptome of Treg resistant HLA-DR+ effector CD4+ T cells isolated from TB subjects with that of the Treg sensitive fraction depleted of HLA-DR+CD4+ T cells, we provided first evidence that HLA-DR+ T effectors from TB express a number of pro-inflammatory cytokines including IL-2, IFNγ, CSF2, IL-17A and IL-22 (Figure 3). This exaggerated cytokine profile was noted in T effectors stimulated with both Mtb antigen as well as polyclonal stimulation [61]. Both IFNγ and IL-17A, although crucial for Mtb control [92, 93], are also recognized to counter-regulate Treg development and function and their exaggerated expansion therefore, could be one mechanism for Teff resistance to Treg control [94-96].