Leishmania spp. are intracellular protozoan parasites
that are
delivered within the dermis of their vertebrate hosts. Within
this peripheral tissue and the draining lymph node, they find and/or
rapidly create dynamic microenvironments that
determine their ultimate fate, namely their more or less successful expansion,
and favour their transmission to another
vertebrate host though a blood-feeding vector. Depending on their genetic
characteristics as well as the genetic make-up
of their hosts, once within the dermis Leishmania spp. very
rapidly drive and maintain sustained T cell-dependent immune
responses that arbitrate their ultimate fate within their hosts. The
analysis of the parasitism exerted by Leishmania major
in mice of different genetic backgrounds has allowed us to recognize
some of the early and late mechanisms driven by this
parasite that lead to either uncontrolled or restricted parasitism.
Uncontrolled parasitism by Leishmania major characterizing mice
from a few inbred strains (e.g. BALB/c) is associated with the expansion
of parasite reactive Th2 CD4
lymphocytes and results from their rapid and sustained activity. In
contrast, restricted parasitism characteristic of mice
from the majority of inbred strains results from the development of a
polarized parasite-specific Th1 CD4 response. This
murine model of infection has already been and will continue to be
particularly instrumental in dissecting the rules
controlling the pathway of differentiation of T cells in vivo.
In the long run, the understanding of these rules should
contribute to the rational development of novel immunotherapeutic
interventions against severe infectious diseases.