CTLA-4 ligands are required to induce an in vivo interleukin 4 response to a gastrointestinal nematode parasite

• Published in: The Journal of experimental medicine 1994-08, Vol.180 (2), p.693-698
• Main Authors: PIN LU, XIA DI ZHOU, CHEN, S.-J, MOORMAN, M, MORRIS, S. C, FINKELMAN, F. D, LINSLEY, P, URBAN, J. F, GAUSE, W. C
• Format: Article
• Language: English
• Subjects: Abatacept; Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens, CD; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; B-Lymphocytes - immunology; Biological and medical sciences; CTLA-4 Antigen; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Heligmosomatoidea - immunology; Immunobiology; Immunoconjugates; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Interleukin-4 - immunology; Intestinal Diseases, Parasitic - immunology; Intestinal Diseases, Parasitic - parasitology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Organs and cells involved in the immune response; Recombinant Fusion Proteins - metabolism; Signal Transduction; Strongylida Infections - immunology; Strongylida Infections - parasitology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.180.2.693

The costimulatory signal provided to T cells through CTLA-4-ligand interactions is required for T cell activation resulting in increased interleukin 2 (IL-2) production in vitro, but its role in the production of IL-4 and other cytokines is unclear and few in vivo studies have been performed to confirm results of in vitro experiments. We have examined the in vivo effects of blocking CTLA-4 ligands on the T helper cell 2 (Th2)-associated mucosal immune response that follows oral infection of mice with the nematode parasite, Heligmosomoides polygyrus. CTLA-4Ig administration inhibited H. polygyrus-induced increases in mesenteric lymph node (MLN) B cell major histocompatibility complex class II expression and size and T cell-derived IL-4 gene expression. In addition, CTLA-4 immunoglobulin (Ig) partially blocked increased IL-3, IL-5, and IL-9 cytokine gene expression in Peyer's patch (PP) and MLN 8 d after primary inoculation of mice with the parasite. Increases in the number of IL-4- but not IL-5-secreting cells were also inhibited by CTLA-4Ig. H. polygyrus-induced elevations in serum IgE levels but not blood eosinophils, were markedly inhibited by CTLA-4Ig. These results suggest that stimulation of CD28 and/or CTLA-4 is required for T cell priming leading to IL-4 cytokine production, B cell activation, and IgE secretion during a Th2-like, mucosal immune response to a nematode parasite.