These observations make possible to hypothesize that expansion of CXCR3+CCR6− CD4+ T cells, rather than representing the main immunological basis of TB-IRIS, may be driven by an underlying augmentation of pro-inflammatory innate mediators prior to ART in TB-HIV patients with high microbial burden and who are at a very high risk of developing this syndrome. The gene discussed is CXCR3; the disease is tuberculosis.