Genetic Control of the T Cell Response to Leishmania Major Infection

Abstract

Cutaneous infection of most inbred mouse strains with the protozoan parasite, Leishmania major, leads to a localized lesion that is contained and resolved primarily by CD4⁺ Th1 cells (1,2). Th1 cells secrete the potent macrophage activator IFN-γ, thus stimulating effective killing of this parasite (1,3). A few inbred mouse strains, such as BALB/c and SWR, fail to control parasite replication. This failure results in progressive lesion development, spread to visceral organs and eventual death. Highly susceptible BALB/c mice have been shown to make a strong immune response, but one that is dominated by CD4⁺ Th2 cells (4), which inhibit macrophage activation by producing IL-4, IL-10 and IL-13 (5). This sharp delineation of Th1 and Th2 responses has made L. major infection a useful model for studying the control of functional differentiation in CD4⁺ T cells. The clear strain differences in the response to L. major also offer the opportunity to study the genetic factors that determine whether an animal can mount a protective or a pathogenic immune response to this infection.