TB granuloma: CD30 co-stimulation for CD4+ T cell co-operation

Abstract

Tuberculosis granuloma T cells express an array of mediators including the CD30 co-stimulatory receptor and its ligand, CD153. CD4 T effector cells require signals through CD30, potentially provided co-operatively by other T cells, to completely differentiate and protect against disease (Foreman et al., 2023. J. Exp. Med.https://doi.org/10.1084/jem.20222090).

Insights from Abigail R. Gress and Tyler D. Bold.

T cells require CD30 expression to undergo Th1 differentiation and mediate protection. Mixed bone marrow chimeras revealed that the protective effect of T cell–derived CD153 in TB is mediated through signals received by other T cells expressing the cognate co-stimulatory receptor CD30. T cells deficient in CD30 therefore fail to undergo Th1 differentiation, even in the context of an infection where wild-type T cells are present. In contrast, CD153-deficient cells can complete Th1 differentiation due to their retained expression of CD30 and the compensatory expression of CD153 by wild-type cells. A star indicates a productive signaling interaction received by CD4 T cells through CD30, which results in Th1 differentiation; an X indicates the absence of such a signal and the failure of complete differentiation.