Article

The Development of Effector T Cell Subsets in Murine Leishmania Major Infection

Department of Medicine, University of California, San Francisco 94143, USA.
Ciba Foundation symposium 02/1995; 195:110-7; discussion 117-22. DOI: 10.1002/9780470514849.ch8
Source: PubMed

ABSTRACT

Leishmania major infection has proven an exceptional model for CD4+ subset development in inbred mice. Most strains contain infection coincident with the appearance of T helper 1 (Th1) cells that produce gamma-interferon (IFN-gamma) required for macrophage activation. In contrast, mice on the BALB background are unable to control infection due to the development of Th2 cells that produce counter-regulatory cytokines, particularly interleukin 4 (IL-4), capable of abrogating the effects of IFN-gamma. Selective gene disruption studies in mice have illustrated critical components of the host response to L. major. Mice deficient in beta 2 microglobulin, which have no major histocompatibility complex (MHC) class I or CD8+ T cells, control infection as well as wild-type mice, whereas mice deficient in MHC class II (and CD4+ T cells) suffer fatal infection. Mice with disruption of the gene coding IFN-gamma are also incapable of containing infection, reflecting absolute requirements for this cytokine. A number of interventions have been demonstrated to abrogate Th2 cell development in BALB mice, enabling these mice to control infection. Each of these--IL-12, anti-IL-4, anti-IL-2, anti-CD4 and CTLA4-Ig--has in common the capacity to make IL-4 rate limiting at the time of CD4+ cell priming.

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    • "Studies show that the early production of IL-4 by unique population of CD4 + T cells promotes the development and expansion of Th2 cells in the susceptible mice (Scott, 1989; Scott et al., 1989; Reiner and Locksley, 1995; Himmelrich et al., 2000). These cells respond to peptides derived from the Leishmania homolog of activated protein kinase (LACK) protein by producing high levels of IL-4 leading to concomitant expansion of Th2 cells (Mougneau et al., 1995). "
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    • "preferential induction of CD4 1 T helper cell subpopula - tions , so - called T helper 1 ( TH1 ) and T helper 2 ( TH2 ) subpopulations . According to this proposed model , based on the dichotomy of CD4 1 T cells , TH1 cells producing mainly IFN - g are related to protection and TH2 cells produ - cing IL - 4 , IL - 5 and IL - 10 to susceptibility ( Locksley et al . , 1995 ; Reiner and Locksley , 1995 ) . However , in addition to CD4 1 T cells , CD8 1 T cells also produce IFN - g In resistant C57 BL / 6 mice infected with L . ( L . ) amazonensis , when CD8 1 T lymphocytes were eliminated by anti - CD8 anti - body and complement , IFN - g production was reduced by 77% , indicating that CD8 1 T cells produc"
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    • "preferential induction of CD4 1 T helper cell subpopula - tions , so - called T helper 1 ( TH1 ) and T helper 2 ( TH2 ) subpopulations . According to this proposed model , based on the dichotomy of CD4 1 T cells , TH1 cells producing mainly IFN - g are related to protection and TH2 cells produ - cing IL - 4 , IL - 5 and IL - 10 to susceptibility ( Locksley et al . , 1995 ; Reiner and Locksley , 1995 ) . However , in addition to CD4 1 T cells , CD8 1 T cells also produce IFN - g In resistant C57 BL / 6 mice infected with L . ( L . ) amazonensis , when CD8 1 T lymphocytes were eliminated by anti - CD8 anti - body and complement , IFN - g production was reduced by 77% , indicating that CD8 1 T cells produc"

    Full-text · Article · Aug 1998 · Parasitology International
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