T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.
Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation.
Langley
J G
JG
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Boros
D L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000209:etiology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D051381:Rats; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1