Bovine type 1 and type 2 responses

The Th1/Th2 paradigm has provided a useful framework for understanding the observed bias in immune responses that are often dominated by either cell-mediated or humoral responses, and for devising therapeutic strategies to stimulate T cell- or antibody-mediated immunity. However this paradigm is an oversimplification of a much more complex immunoregulatory network. Studies with bovine Th cell clones and immunoregulatory cytokines support this viewpoint. This paper highlights the progress that has been made in defining type 1 and type 2 responses in cattle. Evidence is presented for the presence of different subtypes of antigen-specific Th cell clones of cattle which constitute a spectrum of cell phenotypes, and for cytokine-mediated regulation of Th cell responses that differs from that observed in mice. The majority of over 60 parasite antigen-specific Th cell clones coexpress IL-4 and IFN-γ, and polarized cytokine profiles were rarely observed. Furthermore, IL-2 and IL-10 expression was not restricted to IFN-γ or IL-4-producing cells, respectively. This lack of coordinate regulation of ``Th1ʹʹ and ``Th2ʹʹ cytokines strengthens the emerging viewpoint that Th1 and Th2 responses, per se, do not typify the immune response to most pathogens. In addition, we provide evidence that major regulatory cytokines, IL-4, IL-10, and IL-12, do not selectively exert their negative (IL-4 and IL-10) or positive (IL-12) effects on Th1-like cells.