Lack of Th1 or Th2 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 µm synthetic microspheres. This particulate antigen was efficiently presented to T cells by macrophages but not by B lymphocytes. BALB/c
... 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-γ) 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(I):(C) or of IL-12 induced a strong activation of T h 1 cells, as shown by an up-regulated IFN-γ 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.