The Journal of Immunology, Vol 146, Issue 11 3929-3936, Copyright © 1991 by American Association of Immunologists

ARTICLES

Initiation of delayed-type hypersensitivity by low doses of monoclonal IgE antibody. Mediation by serotonin and inhibition by histamine

W Ptak, GP Geba and PW Askenase
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.

Elicitation of delayed-type hypersensitivity (DTH) responses by DTH effector T cells requires a prior phase of DTH initiation. This consists of an immediate hypersensitivity-like response mediated by Ag- specific DTH-initiating factors that are analogous to IgE antibodies in that they sensitize tissue mast cells for release of the vasoactive amine serotonin (5-HT). Experiments were conducted to determine whether IgE mAb injected i.v., or 5-HT injected locally, could initiate DTH. It was found that small doses of IgE (1 microgram/mouse), or of 5-HT (50 to 500 ng locally), which mediated small immediate responses, were optimal for DTH initiation. Even lower doses of IgE (10 ng/mouse), or of 5-HT (5 ng locally), which did not mediate macroscopically measurable immediate responses, were capable of DTH initiation. Higher doses of IgE (10 to 100 micrograms/mouse), which mediated large immediate responses, were not able to initiate DTH. A similar dose response for DTH initiation was found with IgG1 mAb, which is another mast cell-sensitizing isotype of Ig. The inability of high doses of IgE or IgG1 to mediate DTH initiation was probably caused by local release of large inhibitory amounts of histamine, because systemic treatment with the histamine-2 receptor antagonist cimetidine allowed high doses of IgE to initiate DTH. Thus, IgE and IgG1 antibodies could initiate DTH via release of small amounts of 5-HT, but simultaneous release of large amounts of histamine were inhibitory, probably via an effect on histamine-2 receptors of recruited T cells. We concluded the following: 1) IgE or IgG1 antibodies can initiate DTH; 2) DTH initiation need not be associated with macroscopically detectable early responses; 3) mast cell release of 5-HT acts positively whereas release of histamine acts negatively in murine DTH; 4) Ag-specific factors are not the only mechanism of DTH initiation.

This article has been cited by other articles:

				R. K. Morgan, B. McAllister, L. Cross, D. S. Green, H. Kornfeld, D. M. Center, and W. W. Cruikshank Histamine 4 Receptor Activation Induces Recruitment of FoxP3+ T Cells and Inhibits Allergic Asthma in a Murine Model J. Immunol., June 15, 2007; 178(12): 8081 - 8089. [Abstract] [Full Text] [PDF]

				M. Leon-Ponte,, G. P. Ahern, and P. J. O'Connell Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor Blood, April 15, 2007; 109(8): 3139 - 3146. [Abstract] [Full Text] [PDF]

				A. Itakura, M. Szczepanik, R. A. Campos, V. Paliwal, M. Majewska, H. Matsuda, K. Takatsu, and P. W. Askenase An Hour after Immunization Peritoneal B-1 Cells Are Activated to Migrate to Lymphoid Organs Where within 1 Day They Produce IgM Antibodies That Initiate Elicitation of Contact Sensitivity J. Immunol., December 1, 2005; 175(11): 7170 - 7178. [Abstract] [Full Text] [PDF]

				S. Nakae, H. Suto, M. Kakurai, J. D. Sedgwick, M. Tsai, and S. J. Galli Mast cells enhance T cell activation: Importance of mast cell-derived TNF PNAS, May 3, 2005; 102(18): 6467 - 6472. [Abstract] [Full Text] [PDF]

				J. M. Hwang, J. Yamanouchi, P. Santamaria, and P. Kubes A Critical Temporal Window for Selectin-dependent CD4+ Lymphocyte Homing and Initiation of Late-Phase Inflammation in Contact Sensitivity J. Exp. Med., May 3, 2004; 199(9): 1223 - 1234. [Abstract] [Full Text] [PDF]

				R. A. Campos, M. Szczepanik, A. Itakura, M. Akahira-Azuma, S. Sidobre, M. Kronenberg, and P. W. Askenase Cutaneous Immunization Rapidly Activates Liver Invariant V{alpha}14 NKT Cells Stimulating B-1 B Cells to Initiate T Cell Recruitment for Elicitation of Contact Sensitivity J. Exp. Med., December 15, 2003; 198(12): 1785 - 1796. [Abstract] [Full Text] [PDF]

				M. Szczepanik, M. Akahira-Azuma, K. Bryniarski, R. F. Tsuji, I. Kawikova, W. Ptak, C. Kiener, R. A. Campos, and P. W. Askenase B-1 B Cells Mediate Required Early T Cell Recruitment to Elicit Protein-Induced Delayed-Type Hypersensitivity J. Immunol., December 1, 2003; 171(11): 6225 - 6235. [Abstract] [Full Text] [PDF]

				R. F. Tsuji, M. Szczepanik, I. Kawikova, V. Paliwal, R. A. Campos, A. Itakura, M. Akahira-Azuma, N. Baumgarth, L. A. Herzenberg, and P. W. Askenase B Cell-dependent T Cell Responses: IgM Antibodies Are Required to Elicit Contact Sensitivity J. Exp. Med., November 18, 2002; 196(10): 1277 - 1290. [Abstract] [Full Text] [PDF]

				H. Yokozeki, M. Ghoreishi, S. Takagawa, K. Takayama, T. Satoh, I. Katayama, K. Takeda, S. Akira, and K. Nishioka Signal Transducer and Activator of Transcription 6 Is Essential in the Induction of Contact Hypersensitivity J. Exp. Med., March 20, 2000; 191(6): 995 - 1004. [Abstract] [Full Text] [PDF]