Lessons from Leishmania: a model for investigations of CD4+ subset differentiation.
Infection of inbred mice with Leishmania major remains the best model of human infection with visceralizing Leishmania that cause kala-azar. Immunologic investigations have correlated the outcome of disease with expansion of different subsets of CD4+ cells, designated Th1 and Th2. Although the capacity of fixed effector Th1 and Th2 populations to mediate the diverse outcomes of disease through the release of soluble cytokines, particularly IFN-gamma and IL-4, has been demonstrated, the mechanisms by which these subsets become established during infection have not been delineated. This review focuses on known features of CD4+ differentiation using other experimental models, and proposes that genetic susceptibility to Leishmania can occur if the host has a Th2 precursor cell in the memory configuration prior to the time of exposure to organisms, perhaps in response to cross-reactive self-peptides. The hypothesis can explain a number of puzzling observations in both murine and human disease due to these organisms and makes several predictions amenable to experimental testing.
Department of Medicine, University of California, San Francisco 94143-0654.
S L
SL
Reiner
R M
RM
Locksley
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D006801:Humans; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000502:physiology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D015847:Interleukin-4