Analysis of inducible costimulatory molecule participation during the induction and elicitation of granulomatous responses to mycobacterial and schistosomal antigens

• Published in: Cellular Immunology Vol. 237; no. 1; pp. 45 - 54
• Main Authors: Stolberg, Valerie R., Chiu, Bo-chin, Komuniecki, Eric, Freeman, Christine M., Chensue, Stephen W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2005
• Subjects: Animals; Antigens, Bacterial - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Helminth - immunology; Costimulation; Cytokines; Cytokines - biosynthesis; Cytokines - immunology; Female; Flow Cytometry; Granuloma - immunology; Granuloma - microbiology; Inducible T-Cell Co-Stimulator Protein; Inflammation; Mice; Mice, Inbred CBA; Mycobacteriaceae - immunology; Mycobacterium; Parasitic-helminth; Schistosoma mansoni; Schistosoma mansoni - immunology; Th1 Cells - immunology; Th1/Th2 cells; Th2 Cells - immunology; Th1/Th2 cells; Inflammation; Cytokines; Costimulation; Parasitic-helminth
• ISSN: 0008-8749; 1090-2163; 1365-2567
• DOI: 10.1016/j.cellimm.2005.09.005

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 IFNγ 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.