Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers

• Published in: The Journal of experimental medicine Vol. 190; no. 8; pp. 1115 - 1122
• Main Authors: Walker, L S, Gulbranson-Judge, A, Flynn, S, Brocker, T, Raykundalia, C, Goodall, M, Förster, R, Lipp, M, Lane, P
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 18.10.1999
• Subjects: Abatacept; Animals; Antigens, CD; Antigens, Differentiation - immunology; CD28 antigen; CD28 Antigens - genetics; CD28 Antigens - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Count; Cell Movement; CTLA-4 Antigen; CTLA4-Ig protein; CXCR5 protein; Flow Cytometry; Gene Expression Regulation; Germinal Center - immunology; germinal centers; Humans; Immunoconjugates; immunoglobulin G1; Integrin alphaXbeta2 - genetics; Integrin alphaXbeta2 - immunology; L-Selectin - immunology; Mice; Mice, Transgenic; Original; Receptors, Chemokine; Receptors, CXCR5; Receptors, Cytokine - immunology; Receptors, OX40; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins - immunology; RNA, Messenger - metabolism; Signal Transduction - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; Up-Regulation
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.190.8.1115

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.