(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].