Evolution of CD4 T-cell subsets following infection of naive and memory immune mice with Mycobacterium tuberculosis.

We report here that during the course of an experimental infection of mice with Mycobacterium tuberculosis, the differential expression of the cell surface antigens CD44 and CD45RB could be used to delineate CD4+ T cells into four phenotypically distinct subsets. The major subset present was designated CD44lo/CD45RBhi and is associated with naive or resting T cells. The three remaining subsets expressed increased levels of the CD44 antigen as the infection progressed and could therefore be considered to be in an activated state. These activated populations could be further divided on the basis of their variable expression of the CD45RB antigen. These populations were designated CD44hi/CD45RBhi, CD44hi/CD45RBlo, and CD44hi/CD45RBneg. Kinetic studies of the emergence of these populations indicated that these subsets arose sequentially from the naive population at times associated with the peak expression of acquired specific resistance. In further studies, in an attempt to associate either the CD44hi/CD45RBlo or the CD44hi/CD45RBneg population with acquired immunologic memory of tuberculosis infection, draining lymph nodes of challenged memory immune animals were analyzed for the accumulation of the CD4+ subsets. The accumulation of both the CD44hi/CD45RBlo and the CD44hi/CD45RBneg populations was observed, but the CD44hi/CD45RBlo population was enriched in a manner consistent with the rapid accumulation of memory T cells during the anamnestic response. While functional roles for each of these subsets remain to be determined, these data provide the first evidence for the evolution of multiple, phenotypically distinct CD4+ T-cell subsets during the in vivo response to an experimental mycobacterial infection.