Lack of T(h)1 or T(h)2 polarization of CD4(+) T cell response induced by particulate antigen targeted to phagocytic cells

Several factors are involved in the selective activation of T(h)1 or T(h)2 subset of CD4(+) T cells, such as the type of antigen-presenting cells, the dose of antigen, the route of immunization, etc. To analyze the influence of accessory cells on T(h)1/T(h)2 cell differentiation, we used a particulate antigen prepared by covalent linkage of hemocyanin (LH) to 1 mu m synthetic microspheres. This particulate antigen was efficiently presented to T cells by macrophages but not by B lymphocytes, BALB/c mice immunized either with soluble LH in alum or with particulate LH without adjuvant produced both T(h)1 (IL-2 and IFN-gamma) and T(h)2 (IL-4 and IL-5) cytokines, Moreover, mice primed either with soluble or particulate LH secreted higher levels of IgG1- than of IgG2a-specific antibodies. The induction of this cytokine profile response was independent of the route of administration of the antigen, and was observed both in BALB/c and C57BL/6 mice. In contrast, immunization of mice with particulate LH in the presence of poly(l):(C) or of IL-12 induced a strong activation of T(h)1 cells, as shown by an up-regulated IFN-gamma production, and by decreased IL-4 and IL-5 levels associated to a greatly enhanced IgG2a antibody response. These results therefore demonstrate that targeting the antigen to phagocytic cells is not sufficient to stimulate a polarized T-h response and that environmental cytokines play the major role in the selective activation of T(h)1 cells. This study provides important conclusions for the development of new vaccines and shows that particulate antigen associated with appropriate cofactor can selectively activate T(h)1 cells.