Methods for Diagnosing and Treating Mycobacterium tuberculosis (Mtb) Infection through Detection of CD153 Expression Level.

Mycobacterium tuberculosis (Mtb) infection continues to be the leading cause of death due to a single infectious agent and poses significant global health challenges. Past research has shown that CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFN(?) production is the primary mechanism of CD4 T cell-mediated protection.

NIAID researchers have discovered that the expression of TNF superfamily molecule CD153 (TNSF8) is required for control of the pulmonary Mtb infection by CD4 T cells. The results have shown that, in Mtb infected mice, CD153 expression is highest on Ag-specific Th1 cells in the lung tissue parenchyma. On the contrary, CD153 deficient mice have developed high pulmonary bacterial loads and succumb early to Mtb infection. In Mtb infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to the blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. Further, in Mtb infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active TB. Since the expression of CD153 by CD4 T cells is a major immune mechanism of host protection against Mtb infection, the discovery can be used to effectively diagnose and treat Mtb infections in the future.