CONTINUOUS REPOPULATION OF LYMPHOCYTE SUBSETS IN TRANSPLANTED MYCOBACTERIAL GRANULOMAS.

Granulomas are the interface between host and mycobacteria, and are crucial for the surivival of both species. While macrophages are the main cellular component of these lesions, different lymphocyte subpopulations within the lesions also play important roles. Lymphocytes are continuously recruited into these inflammatory lesions via local vessels to replace cells that are either dying or leaving; however, their rate of replacement is not known. Using a model of granuloma transplantation and fluorescently labeled cellular compartments we report that, depending on the subpopulation, 10-80%, of cells in the granuloma are replaced within one week after transplantation. CD4(+) T cells specific for Mycobacterium antigen entered transplanted granulomas at a higher frequency than Foxp3(+) CD4(+) T cells by one week. Interestingly, a small number of T lymphocytes migrated out of the granuloma to secondary lymphoid organs. The mechanisms that define the differences in recruitment and efflux behind each subpopulation requires further studies. Ultimately, a better understanding of lymphoid traffic may provide new ways to modulate, regulate, and treat granulomatous diseases.