The Potential Use of Different Vaccination Protocols to Tailor Cytokine Profiles

Abstract

Helper CD4+ T cells, through the production of cytokines, play a central role in the regulation of immune responses. In vitro studies with murine T cell clones have shown the existence of two types of Th cells that could be distinguished on the basis of their cytokine production (Mosmann et al., 1986; Mosmann and Coffman, 1989). The Th1 subset secretes IL-2 and IFN-γ, and preferentially promotes cell-mediated immunity and IgG2a production by B lymphocytes whereas the Th2 subset produces IL-4, IL-5, IL-10 and IL-13, and induces humoral immunity and IgG1 and IgE isotypes production ( Snapper and Paul 1987; Coffman et al, 1986; Thyphronitis et al., 1989; Cocks et al, 1993). In vivo studies revealed that in some infections, these cytokine profiles determine the outcome of the disease, demonstrating that this dichotomy is physiologically relevant (Heinzel et al., 1989; Mielke et al., 1993; Yamamura et al., 1991; Flesch and Kaufmann 1987). In general Thl responses are more effective against some intracellular pathogens (Heinzel et al., 1989; Hsieh et al., 1993), whereas Th2 responses are more appropriate in helminth parasitoses (Sher and Coffman 1992; Urban et al., 1991). Using animal models, it has been shown that in some diseases, the expression of the inappropriate profile can be deleterious and enhance pathology. This is best illustrated with the mouse leishmaniasis model. Animals that in response to infection, develop a Th1 type response, spontaneously heal, as opposed to mice that develop a Th2 response and succumb to the infection (Heinzel et al., 1989). Evolution of several other infectious diseases including T. muris infection in mice (Else et al., 1994), M. leprae infections in humans (Yamamura et al., 1991) and others have been shown to be dependent or associated with the one or the other type of Th responses.