CD30 co-stimulation drives differentiation of protective T cells during Mycobacterium tuberculosis infection

Control of Mycobacterium tuberculosis (Mtb) infection requires generation of T cells that migrate to granulomas, complex immune structures surrounding sites of bacterial replication. Here we compared the gene expression profiles of T cells in pulmonary granulomas, bronchoalveolar lavage, and blood of Mtb-infected rhesus macaques to identify granuloma-enriched T cell genes. TNFRSF8/CD30 was among the top genes upregulated in both CD4 and CD8 T cells from granulomas. In mice, CD30 expression on CD4 T cells is required for survival of Mtb infection, and there is no major role for CD30 in protection by other cell types. Transcriptomic comparison of WT and CD30(-/-) CD4 T cells from the lungs of Mtb-infected mixed bone marrow chimeric mice showed that CD30 directly promotes CD4 T cell differentiation and the expression of multiple effector molecules. These results demonstrate that the CD30 co-stimulatory axis is highly upregulated on granuloma T cells and is critical for protective T cell responses against Mtb infection. Foreman et al. find CD30 is preferentially expressed on granuloma T cells in Mtb-infected macaques. In mice, CD30 drives T cell differentiation and is required for host survival of Mtb infection, showing T cell immunity to Mtb requires CD30-dependent co-stimulation.

Automated summary

CD30 is highly expressed on granuloma T cells in macaques infected with Mtb. In mice, CD30 is essential for T cell differentiation and survival during Mtb infection, indicating that CD30-dependent co-stimulation is necessary for T cell immune responses against Mtb.