In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II: Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39

• Published in: The Journal of experimental medicine 1993-11, Vol.178 (5), p.1567-1575
• Main Authors: FOY, T. M, SHEPHERD, D. M, DURIE, F. H, ARUFFO, A, LEDBETTER, J. A, NOELLE, R. J
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antibodies - pharmacology; Antibody Formation; Antibody production; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - metabolism; B-Lymphocytes - immunology; Biological and medical sciences; CD40 Antigens; CD40 Ligand; Clone Cells; Cricetinae - immunology; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hemocyanins - immunology; Humans; Immunobiology; Immunoglobulin E - analysis; Immunoglobulin E - biosynthesis; Immunoglobulin G - analysis; Immunoglobulin G - biosynthesis; Immunoglobulin G - classification; Immunoglobulin M - analysis; Immunoglobulin M - biosynthesis; Immunosuppression; Immunotherapy, Adoptive; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; T-Lymphocytes - immunology; T-Lymphocytes, Helper-Inducer - immunology; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.178.5.1567

The ligand for CD40 has been recently identified as a 39-kd protein, gp39, expressed on the surface of activated CD4+ T helper cells (Th). In vitro, soluble CD40 and anti-gp39 have been shown to block the ability of Th to activate B cells, suggesting that gp39-CD40 interactions are important to T cell-dependent B cell activation. Here it is shown that in vivo administration of anti-gp39 dramatically reduced both primary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type II antigen, trinitrophenyl-Ficoll. Treatment of mice for 4 d with anti-gp39 inhibited the anti-sheep red blood cell (SRBC) response for at least 3 wk and inhibited the expression of all immunoglobulin isotypes in secondary responses to the protein antigen, keyhole limpet hemocyanin. To examine the direct effect of anti-gp39 on Th function, SRBC-immune Th cells from anti-gp39-treated mice were adoptively transferred and shown to be fully capable of providing help. These results suggest that anti-gp39 treatment does not cause Th deletion or anergy. Anti-gp39 may mediate its profound immunosuppressive effects on humoral immunity by blocking gp39-CD40 interactions. Moreover, these studies establish gp39-CD40 as an important receptor-ligand pair for the targeting of therapeutic antibodies to control thymus-dependent humoral responses.