HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morris, S. C. Articles by Finkelman, F. D. Search for Related Content PubMed PubMed Citation Articles by Morris, S. C. Articles by Finkelman, F. D.

In Vivo IL-4 Responses to Anti-IgD Antibody Are MHC Class II Dependent and ß₂-Microglobulin Independent and Develop Normally in the Absence of IL-4 Priming of T Cells^{1 ,2}

Suzanne C. Morris^*, Robert L. Coffman and Fred D. Finkelman^3,*

^* Division of Immunology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, and Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220; and Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304

A crucial role for CD1-responsive, MHC class II-unrestricted T cells in the generation of T cell IL-4 responses is suggested by the: 1) requirement for IL-4 to prime in vitro IL-4 responses by naive CD4⁺ T cells; 2) ability of TCR cross-linking to induce CD1-responsive T cells, but not conventional naive T cells, to produce IL-4; 3) failure of anti-IgD Ab to induce an IL-4-dependent IgE response in ß₂-microglobulin-deficient mice, which lack CD1; and 4) reported ability of MHC class II-deficient mice to make IgE responses to anti-IgD Ab. In contrast, the Ag specificity of cytokine and Ab responses in anti-IgD-injected mice and the normal IgE responses made by anti-IgD-treated CD1-deficient mice are difficult to reconcile with this view. We now find that the failure of ß₂-microglobulin-deficient mice to make an IgE response to anti-IgD Ab is caused by their rapid degradation of anti-IgD; sustained anti-IgD treatment induces them to make relatively normal IL-4 and IgE responses. Furthermore, in our study, MHC class II-deficient mice make little or no IL-4 or IgE responses to anti-IgD Ab and ß₂-microglobulin-deficient mice make large in vivo IL-4 responses to anti-CD3 mAb. Finally, although IL-4 priming of T cells for IL-4 production is Stat6 dependent, Stat6-deficient mice make normal IL-4 responses to anti-IgD. Thus, CD1-responsive T cells and other ß₂-microglobulin-dependent T cells are not required to prime conventional CD4⁺ T cells to make IL-4 responses to anti-IgD in vivo; in fact, the large IL-4 response made in this system does not require IL-4 priming.

This article has been cited by other articles:

				T. Chitnis, A. D. Salama, M. J. Grusby, M. H. Sayegh, and S. J. Khoury Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo J. Immunol., April 1, 2004; 172(7): 4260 - 4265. [Abstract] [Full Text] [PDF]

				E. E. S. Nieuwenhuis, M. F. Neurath, N. Corazza, H. Iijima, J. Trgovcich, S. Wirtz, J. Glickman, D. Bailey, M. Yoshida, P. R. Galle, et al. Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice PNAS, December 24, 2002; 99(26): 16951 - 16956. [Abstract] [Full Text] [PDF]

				N. Noben-Trauth, J. Hu-Li, and W. E. Paul Conventional, Naive CD4+ T Cells Provide an Initial Source of IL-4 During Th2 Differentiation J. Immunol., October 1, 2000; 165(7): 3620 - 3625. [Abstract] [Full Text] [PDF]

				D. Jankovic, M. C. Kullberg, N. Noben-Trauth, P. Caspar, W. E. Paul, and A. Sher Single Cell Analysis Reveals That IL-4 Receptor/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+ Lymphocytes with a Th2 Cytokine Profile J. Immunol., March 15, 2000; 164(6): 3047 - 3055. [Abstract] [Full Text] [PDF]

				F. D. Finkelman, S. C. Morris, T. Orekhova, M. Mori, D. Donaldson, S. L. Reiner, N. L. Reilly, L. Schopf, and J. F. Urban Jr. Stat6 Regulation of In Vivo IL-4 Responses J. Immunol., March 1, 2000; 164(5): 2303 - 2310. [Abstract] [Full Text] [PDF]

				L. H. Wang, X. Y. Yang, R. A. Kirken, J. H. Resau, and W. L. Farrar Targeted disruption of Stat6 DNA binding activity by an oligonucleotide decoy blocks IL-4-driven TH2 cell response Blood, February 15, 2000; 95(4): 1249 - 1257. [Abstract] [Full Text] [PDF]

				J. M. Brewer, M. Conacher, C. A. Hunter, M. Mohrs, F. Brombacher, and J. Alexander Aluminium Hydroxide Adjuvant Initiates Strong Antigen-Specific Th2 Responses in the Absence of IL-4- or IL-13-Mediated Signaling J. Immunol., December 15, 1999; 163(12): 6448 - 6454. [Abstract] [Full Text] [PDF]

				M. H. Kaplan, A. L. Wurster, S. T. Smiley, and M. J. Grusby3 Stat6-Dependent and -Independent Pathways for IL-4 Production J. Immunol., December 15, 1999; 163(12): 6536 - 6540. [Abstract] [Full Text] [PDF]

				S. Hill, E. Herlaar, A. Le Cardinal, G. van Heeke, and P. Nicklin Homologous Human and Murine Antisense Oligonucleotides Targeting Stat6 . Functional Effects on Germline Cepsilon Transcript Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 728 - 737. [Abstract] [Full Text]

				F. D. Finkelman and S. C. Morris Development of an assay to measure in vivo cytokine production in the mouse Int. Immunol., November 1, 1999; 11(11): 1811 - 1818. [Abstract] [Full Text] [PDF]

				M. E. Payet, E. C. Woodward, and D. H. Conrad Humoral Response Suppression Observed with CD23 Transgenics J. Immunol., July 1, 1999; 163(1): 217 - 223. [Abstract] [Full Text] [PDF]

				S. N. Georas, J. E. Cumberland, T. F. Burke, R. Chen, U. Schindler, and V. Casolaro Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells Blood, December 15, 1998; 92(12): 4529 - 4538. [Abstract] [Full Text] [PDF]