In these studies, IFN gamma-inducing factor (IGIF), unlike IL-12, did not drive Th1 development in BALB/c or C57BL/6 mice, but like IL-1alpha, potentiated IL-12-driven Th1 development in BALB/c mice. IGIF and IL-12 synergized for IFN gamma production from Th1 cells. Unlike IL-1alpha, IGIF had no effect on Th2 cells. IGIF signaled through IRAK, IL-1 receptor-associated kinase, to induce nuclear translocation of p65/p50 NFkappaB in Th1 cells. IL-1alpha had no effect on proliferation, cytokine production, or NFkappaB activation in Th1 cells but activated NFkappaB and proliferation in Th2 cells. Thus, Th1 and Th2 cells may differ in responsiveness and receptor expression for IL-1 family molecules. IGIF and IL-1alpha may differentially amplify Th1 and Th2 effector responses, respectively.

SummaryThe dose of foreign antigen can influence whether a cell-mediated or humoral class ofirm'nune response is elicited, and this may be largely accounted for by the development of CD4 + T helper cells (Th) producing distinct sets of cytokines. The ability of antigen dose to direct the development of a Thl or Th2 phenotype from naive CD4 + T cells, however, has not been demonstrated. In this report, we show that the antigen dose used in primary cultures could directly affect Th phenotype development from naive DOl1.10 TCR-et[3-transgenic CD4 + T cells when dendritic cells or activated B cells were used as the antigen-presenting cells. Consistent with our previous findings, midrange peptide doses (0.3-0.6 p,M) directed the development of Th0/Thl-like cells, which produced moderate amounts of interferon ~/ (IFN-y). As the peptide dose was increased, development of Thl-like cells producing increased amounts of IFN-'y was initially observed. At very high (>10 p,M) and very low (<0.05 b~M) doses of antigenic peptide, however, a dramatic switch to development of Th2-1ike cells that produced increasing amounts of interleukin 4 (IL-4) and diminishing levels of IFN-y was observed. This was true even when highly purified naive, high buoyant density CD4 + LECAM-1 hi T cells were used, ruling out a possible contribution from contaminating "memory" phenotype CD4 + T cells. Neutralizing anti-IL-4 antibodies completely inhibited the development of this Th2-like phenotype at both high and low antigen doses, demonstrating a requirement for endogenous IL-4. Our findings suggest that the antigen dose may affect the levels of endogenous cytokines such as IL-4 in primary cultures, resulting in the development of distinct Th cell phenotypes.

IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity. Here we describe a mouse Fc receptor, designated Fc alpha/microR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity. Fc alpha/microR is constitutively expressed on the majority of B lymphocytes and macrophages. Cross-linking Fc alpha/microR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor. Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes.

NK cells use a variety of receptors to detect abnormal cells, including