A Single Treatment with Adjuvant Stimulates Th1-Like Cytokines and Downregulates Th2-Mediated Primary and Secondary Allergic Responses

Abstract

CD4+ T cells play a central role in most effective immune responses to antigens and pathogens. Since the phenotype of CD4+ T cells induced defines the nature of the subsequent immune response, designing vaccines which favor the appropriate T cell subset is of critical importance. Two subsets of mature Th cells, Th1 and Th2, have been distinguished based upon the pattern of cytokines they produce (Mosmann and Coffman, 1989; Brown et al., 1989). Antigen-presenting cells (APC), which first contact and process antigens, present them to naive “Th0” cells in the context of certain cytokines and costimulatory signals. The microenvironment encountered by naive Th0 cells in conjuction with antigens influences their development towards a Thl or Th2 direction. In particular, IL-12, IFN-γ and IFN-α favor Th1 cell development, whereas IL-4 promotes differentiation into Th2 cells (Swain, 1993; Hsieh et al, 1993a; Seder et al., 1993; Brinkmann et al., 1993; Wenner et al., 1996). Differentiated, antigen-specific Thl cells produce IFN-γ, IL-2 and TNF-6 (Abbas et al., 1996). Th1 cells promote DTH and complement-fixing, IgG2a antibody production in mice, while the Th2 subset promotes the formation of IgG1 and allergy-mediating IgE antibodies in mice (Finkelman et al., 1990; Snapper and Paul, 1987; Finkelman et al., 1988b; Finkelman et al., 1988a; Finkelman et al, 1986). Evidence for Thl and Th2-like populations exists in human diseases such as leprosy, leishmaniasis, HIV (progression), atopy, and asthma (Secrist et al., 1993; Parronchi et al, 1991; Clerici and Shearer, 1993; Yamamura et al., 1991; Heinzel et al., 1991). Thl and Th2 subsets produce factors which enhance their own development and downregulate each other’s activity (Maggi et al., 1992; Powrie and Coffman, 1993; Schmitt et al., 1994; Swain et al, 1991; Tanaka et al., 1993).