In this article, we show that induction of Th2 cell tolerance prevents antigen-induced eosinophil recruitment into the tissue and IgE antibody production, and that ICAM-1/LFA-1 interaction is involved as a costimulatory signal in inducing T cell tolerance to a soluble antigen. In vivo pretreatment with anti-ICAM-1 monoclonal antibody (mAb), anti-LFA-1 mAb, and a soluble antigen inhibited antigen-induced eosinophil recruitment into the airways and IgE antibody production in mice in an antigen-specific manner. In vitro antigen-induced IL-2, IL-4 and IL-5 production were decreased in spleen cells of the mice pretreated with the two mAbs and the antigen, indicating the induction of both Th1 and Th2 cell tolerance in vivo. These results suggest that the induction of antigen-specific Th2 cell tolerance by allergen immunotherapy with blockade of the ICAM-/LFA-1 interaction would be a rational therapeutic approach to allergic inflammation such as asthma.
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Metzger WJ, Zavala D, Richerson HB, Moseley P, Iwamota P, Monick M, Sjoerdsma K, Hunninghake GW: Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs: Description of the model and local airway inflammation. Am Rev Respir Dis 1987;135: 433–440.
Kay AB, Ying S, Varney V, Gaga M, Durham SR, Moqbel R, Wardlaw AJ, Hamid Q: Messenger RNA expression of the cytokine gene cluster, IL-3, IL-4, IL-5, and GM-CSF in allergen-induced late-phase cutaneous reactions in atopic subjects. J Exp Med 1991;173:775–778.
Durham SR, Ying S, Varney VA, Jacobson MR, Sudderick RM, Mackay IS, Kay AB, Hamid QA: Cytokine messenger RNA expression for IL-3, IL-4, IL-5, and GM-CSF in the nasal mucosa after local allergen provocation: Relationship to tissue eosinophilia. J Immunol 1992;148:2390–2394.
Nakajima H, Iwamoto I, Tomoe S, Matsumura R, Tomioka H, Takatsu K, Yoshida S: CD4+ T lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis 1992;144:374–377.
Mosmann TR, Coffman L: TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145–178.
Mueller DL, Jenkins MK, Schwartz RH: Clonal expansion versus functional clonal inactivation. Annu Rev Immunol 1989;7:455–480.
Schwartz RH: A cell culture model for T lymphocyte clonal anergy. Science 1990;248:1349–1356.
Jenkins MK, Chen C, Jung G, Mueller DL, Schwartz RH: Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody. J Immunol 1990;144:16–22.
Williams ME, Lichtman AH, Abbas AK: Anti-CD3 antibody induces unresponsiveness to IL-2 in Th1 clones but not in Th2 clones. J Immunol 1990;144:1208–1214.
Gilbert KM, Hoang KD, Weigle WO: Th1 and Th2 clones differ in their response to a tolerogenic signal. J Immunol 1990;144:2063–2071.
De Wit D, Van Mechelen M, Ryelandt M, Figueiredo AC, Abramowicz D, Goldman M, Bazin H, Urbain J, Leo O: The injection of deaggregated gamma globulins in adult mice induces antigen-specific unresponsiveness of T helper type 1 but not type 2 lymphocytes. J Exp Med 1992;175:9–14.
Burstein HJ, Shea CM, Abbas AK: Aqueous antigens induce in vivo tolerance selectively in IL-2 and IFN-γ producing (Th1) cells. J Immunol 1992;148:3687–3691.
Nakao A, Nakajima H, Nishimura T, Iwamoto I: Induction of T cell tolerance by pretreatment with anti-ICAM-1 and anti-LFA-1 antibodies prevents antigen-induced eosinophil recruitment into the mouse airways. J Immunol 1994;153:5819–5825.
Schwartz RH: Costimulation of T lymphocytes: The role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992;71:1065–1068.
Jenkins MK, Johnson JG: Molecules involved in T cell costimulation. Curr Opin Immunol 1993;5: 361–367.
Robey E, Allison JP: T cell activation: Integration of signals from the antigen receptor and costimulatory molecules. Immunol Today 1995; 16:306–310.
Pages F, Ragueneau M, Rottapel R, Truneh A, Nunes J, Imbert J, Olive D: Binding of phosphatidyl-inositol-3-OH kinase to CD28 is required for T cell signalling. Nature 1994;369: 327–329.
Su B, Jacinto E, Hibi M, Kallunki T, Karin M, Ben-Neriah Y: JNK is involved in signal integration during costimulation of T lymphocytes. Cell 1994;77:727–736.
Kang S, Beverly B, Tran A, Brorson K, Schwartz RH, Lenardo MJ: Transactivation by AP-1 is a molecular target of T cell clonal anergy. Science 1992;257:1134–1138.
Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T cell clones Nature 1992;356:607–609.
Siu G, Hedrick SM, Brian AA: Isolation of the murine intercellular adhesion molecule-1 (ICAM-1) gene: ICAM-1 enhances antigen-specific T cell activation. J Immunol 1989; 143:3813–3820.
van Seventer GA, Shimizu Y, Horgan KJ, Shaw S: The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 1990;144:4579–4586.
Damle NK, Klussman K, Linsley PS, Aruffo A: Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol 1992;148:1985–1992.
Wacholtz MC, Patel SS, Lipsky PE: Leukocyte function-associated antigen 1 is an activation molecule for human T cells. J Exp Med 1989;170: 431–448.
van Seventer GA, Bonvini E, Yamada H, Conti A, Stringfellow S, June CH, Shaw S: Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T cells by LFA-1 ligand ICAM-1 involves prolonged inositol phospholipid hydrolysis and sustained increase of intracellular Ca2+ levels. J Immunol 1992;149:3872–3880.
June CH, Ledbetter JA, Gillespie MM, Lindsten T, Thompson CB: T cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol 1987; 7:4472–4481.
Damle NK, Klussman K, Linsley PS, Aruffo A, Ledbetter JA: Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the CD28 counter-receptor B7. J Immunol 1992;149: 2541–2548.
Finkelman FD, Katona IM, Urban JF, Snapper CM, Ohara J, Paul WE: Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1. Proc Natl Acad Sci USA 1986;83:9675–9678.
Briner TJ, Kuo M, Keating KM, Rogers BL, Greenstein JL: Peripheral T cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergenFel d I. Proc Natl Acad Sci USA 1993;90:7608–7612.
Romball CG, Weigle WO: In vivo induction of tolerance in murine CD4+ T cell subsets. J Exp Med 1993;178:1637–1644.
Morris SC, Lees A, Holmes JM, Jeffries RDA, Finkelman FD: Induction of B cell and T cell tolerance in vivo by anti-CD23 mAb. J Immunol 1994;152:3768–3776.
Rocken M, Urban J, Shevach EM: Antigen-specific activation, tolerization, and reactivation of the interleukin 4 pathway in vivo. J Exp Med 1994;179:1885–1893.
Springer TA: Adhesion receptors of the immune system. Nature 1990; 346:425–434.
Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994;76:301–314.
Ramsdell F, Fowlkes BJ: Maintenance of in vivo tolerance by persistence of antigen. Science 1992;257: 1130–1134.
Rocha B, Tanchot C, von Boehmer H: Clonal anergy blocks in vivo growth of mature T cells and can be reversed in the absence of antigen. J Exp Med 1993;177:1517–1521.
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Iwamoto, I., Nakao, A. Induction of Th2 cell tolerance to a soluble antigen by blockade of the LFA-1-dependent pathway prevents allergic inflammation. Immunol Res 14, 263–270 (1995). https://doi.org/10.1007/BF02935624
- Th2 cell tolerance
- Soluble antigen
- Allergic inflammation
- Th2 cell tolerance
- Soluble antigen
- Allergic inflammation