LACK OF T(H)1 OR T(H)2 POLARIZATION OF CD4(-CELL RESPONSE INDUCED BY PARTICULATE ANTIGEN TARGETED TO PHAGOCYTIC-CELLS() T)

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 hemocya nin (LH) to 1 mu m synthetic microspheres. This particulate antigen wa s efficiently presented to T cells by macrophages but not by B lymphoc ytes, BALB/c mice immunized either with soluble LH in alum or with par ticulate 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 IgG 2a-specific antibodies. The induction of this cytokine profile respons e was independent of the route of administration of the antigen, and w as 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-1 2 induced a strong activation of T(h)1 cells, as shown by an up-regula ted IFN-gamma production, and by decreased IL-4 and IL-5 levels associ ated to a greatly enhanced IgG2a antibody response. These results ther efore demonstrate that targeting the antigen to phagocytic cells is no t sufficient to stimulate a polarized T-h response and that environmen tal 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 app ropriate cofactor can selectively activate T(h)1 cells.