CYTOKINE SECRETION AND ADHESION MOLECULE EXPRESSION BY GRANULOMA T-LYMPHOCYTES IN MYCOBACTERIUM-AVIUM INFECTION

Mice experimentally infected with Mycobacterium avium develop a chroni c disease characterized by widespread noncaseating granulomas. In this report, we describe the phenotype and cytokine secretion profile of t hese granuloma-infiltrating effector T lymphocytes. In response to spe cific antigen, granuloma T cells and to a lesser extent, spleen cells secrete interferon-gamma, but no interleukin-4 or -5. The importance o f this Th1-like response to the host was demonstrated by the massively increased bacterial load and lethal disease in interferon-gamma knock out mice. One function of localized cytokine secretion is to recruit i nflammatory T cells bearing surface adhesion molecules complementary t o counter-receptors on vascular endothelial cells, Granuloma T cells e xpress high levels of these pro-inflammatory adhesion molecules but ha ve down-regulated their expression of L-selectin (CD62L). The expressi on of these adhesion molecules on granuloma-infiltrating T lymphocytes would alter the migration pathway of these cells and is likely to be important in facilitating the traffic of effector T cells to the granu lomatous inflammatory site, In addition, T cells from Schistosoma mans oni granulomas express the same set of adhesion molecules, showing tha t this phenotype is not specifically dependent upon the Th1 pattern of cytokine secretion.