Cytokine secretion and adhesion molecule expression by granuloma T lymphocytes in Mycobacterium avium infection

• Published in: The American journal of pathology Vol. 148; no. 6; pp. 1935 - 1948
• Main Authors: Sacco, RE, Jensen, RJ, Thoen, CO, Sandor, M, Weinstock, J, Lynch, RG, Dailey, MO
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.06.1996; American Society for Investigative Pathology
• Subjects: AIDS/HIV; Animals; Antigens, CD - biosynthesis; Biological and medical sciences; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cell Adhesion; Cell Adhesion Molecules - biosynthesis; Cell Division; Cytokines - secretion; Disease Models, Animal; Endothelium, Vascular - immunology; Female; Granuloma - immunology; Granuloma - metabolism; Granuloma - pathology; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Liver - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium avium-intracellulare Infection - immunology; Mycobacterium avium-intracellulare Infection - metabolism; Mycobacterium avium-intracellulare Infection - pathology; Receptors, Interleukin-2 - biosynthesis; Schistosomiasis mansoni - immunology; Selectins - biosynthesis; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Venules - immunology; Immunohistochemistry; Granuloma; Mycobacterial infection; T-Lymphocyte; Bacteria; Immunopathology; Opportunistic infection; Rodentia; Cytokine; Cell adhesion molecule; Mycobacterium avium; AIDS; Immune deficiency; Adhesion; Infection; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Mycobacteriales; Viral disease; Animal; Bacteriosis; Mycobacteriaceae; Actinomycetes
• ISSN: 0002-9440; 1525-2191

Mice experimentally infected with Mycobacterium avium develop a chronic disease characterized by widespread noncaseating granulomas. In this report, we describe the phenotype and cytokine secretion profile of these granuloma-infiltrating effector T lymphocytes. In response to specific antigen, granuloma T cells and, to a lesser extent, spleen cells secrete interferon-gamma, but no interleukin-4 or -5. The importance of this Th1-like response to the host was demonstrated by the massively increased bacterial load and lethal disease in interferon-gamma knockout mice. One function of localized cytokine secretion is to recruit inflammatory T cells bearing surface adhesion molecules complementary to counter-receptors on vascular endothelial cells. Granuloma T cells express high levels of these pro-inflammatory adhesion molecules but have down-regulated their expression of L-selectin (CD62L). The expression 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 granulomatous inflammatory site. In addition, T cells from Schistosoma mansoni granulomas express the same set of adhesion molecules, showing that this phenotype is not specifically dependent upon the Th1 pattern of cytokine secretion.