The current literature on TB-IRIS has therefore relied on analyses of human samples, including plasma cytokine measurements, transcriptome analysis, and in vitro stimulation of peripheral blood mononuclear cells (PBMCs), and has broadly supported a central role of a synergistic interaction of the innate and adaptive immune systems by way of the self-reinforcing responses of dysregulated CD4 T cells and macrophages in the unchecked inflammation of TB-IRIS (Figure 2). Here, CD4 is linked to tuberculosis.