In vivo IL-4 responses to anti-IgD antibody are MHC class II dependent and beta 2-microglobulin independent and develop normally in the absence of IL-4 priming of T cells.
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 beta 2-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 beta 2-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 beta 2-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 beta 2-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.
Morris
S C
SC
Department of Medicine, University of Cincinnati College of Medicine, OH 45267, USA.
Coffman
R L
RL
Finkelman
F D
FD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D006041:Goats; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D007072:Immunoglobulin D / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007275:Injections, Intravenous; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; C039951:anti-IgD; D001613:beta 2-Microglobulin; D015847:Interleukin-4; D007073:Immunoglobulin E