RNA sequencing of flow-sorted lung parenchymal CD226+ and CD226- CD8 T cells from mice chronically infected with Mycobacterium tuberculosis

Lung CD8⁺ T cells induced during chronic tuberculosis exhibit functional heterogeneity, comprising both effector and exhausted states. CD226 is the most differentially expressed gene distinguishing effector from exhausted CD8⁺ T cells. Functionally, CD226 serves as a costimulatory molecule that promotes recognition of Mtb-infected macrophages. Loss of CD226 expression correlates with the onset of CD8⁺ T cell exhaustion during tuberculosis. This study compared lung parenchymal (CD45-IV-) antigen-experienced (CD44+) CD226+ and CD226- CD8 T cells, sorted from C57BL/6 mice infected with Mycobacterium tuberculosis for 24-28 weeks.