title: Analysis of inducible costimulatory molecule participation during the induction and elicitation of granulomatous responses to mycobacterial and schistosomal antigens.
abstract: The contribution of inducible costimulatory molecule (ICOS) to Th1 and Th2 cell-mediated immune responses was examined in well-defined pathogen antigen-elicited models of cell-mediated granuloma formation. Th1 and Th2 granulomas were respectively induced by intravenous challenge of CBA/J mice with Mycobacteria bovis purified protein derivative (PPD) or Schistosoma mansoni egg (SEA) antigen-coated beads. Effects of anti-ICOS blocking antibody on granulomas and lymphoid responses were assessed during elicitation and sensitization. Anti-ICOS treatment during the elicitation abrogated Th1- but not Th2-cell-mediated granuloma formation. Treatment during sensitization augmented SEA-bead granulomas and Th2 cytokines in lymphoid tissue. Anti-ICOS reduced the primary inflammatory response to PPD- but not to SEA-beads, despite comparable induction of ICOS-ligand and ICOS+ T cells. Treatment did not prevent early development of IFNgamma producing cells. Thus, post-activation effector Th1 activity was subject to ICOS blockade and chronic treatment caused diversion to Th2 dominance likely by eroding Th1 effector function or survival.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Stolberg
authors.forename: Bo-chin
authors.initials: BC
authors.lastname: Chiu
authors.forename: Eric
authors.initials: E
authors.lastname: Komuniecki
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freeman
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Chensue
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology / Q000382:microbiology*; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008808:Mice, Inbred CBA; D009159:Mycobacteriaceae / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D000947:Antigens, Helminth; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein