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 i n the generation of T cell IL-4 responses is suggested by the: 1) requ irement for IL-4 to prime in vitro IL-4 responses by naive CD4(+) T ce lls; 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 an ti-IgD Ab to induce an IL-4-dependent IgE response in beta(2)-microglo bulin-deficient mice, which lack CD1; and 4) reported ability of MHC c lass II-deficient mice to make IgE responses to anti-IgD Ab, In contra st, the Ag specificity of cytokine and Ab responses in anti-IgD-inject ed mice and the normal IgE responses made by anti-IgD-treated CD1-defi cient mice are difficult to reconcile with this view, We now find that the failure of beta(2)-microglobulin-deficient mice to make an IgE re sponse 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-defici ent mice make little or no IL-4 or IgE responses to anti-IgD Ab and be ta(2)-microglobulin-deficient mice make large in vivo IL-4 responses t o anti-CD3 mAb, Finally, although IL-4 priming of T cells for IL-4 pro duction is Stat6 dependent, Stat6-deficient mice make normal IL-4 resp onses to anti-IgD, Thus, CD1-responsive T cells and other beta(2)-micr oglobulin-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 l arge IL-4 response made in this system does not require IL-4 priming.