Cytokine secretion and adhesion molecule expression by granuloma T lymphocytes in Mycobacterium avium infection.
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.
Sacco
R E
RE
Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Jensen
R J
RJ
Thoen
C O
CO
Sandor
M
M
Weinstock
J
J
Lynch
R G
RG
Dailey
M O
MO
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012555:Schistosomiasis mansoni / Q000276:immunology; D019087:Selectins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014699:Venules / Q000276:immunology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015375:Receptors, Interleukin-2; D019087:Selectins