Journal article
TGF-β Mediates CTLA-4 Suppression of Cellular Immunity in Murine Kalaazar
The Journal of immunology (1950), Vol.164(4), pp.2001-2008
02/15/2000
DOI: 10.4049/jimmunol.164.4.2001
PMID: 10657651
Abstract
Recent studies indicate important roles for CTLA-4 engagement in T cells, and for TGF-beta production in the immunopathogenesis of murine kalaazar or visceral leishmaniasis, but a functional link between these two pathways in helping intracellular parasite growth is unknown. Here we report that Ag or anti-CD3 activation of splenic CD4+ T cells from visceral leishmaniasis leads to intense CTLA-4-mediated TGF-beta1 production, as assessed either by CTLA-4 blockade or by direct CTLA-4 cross-linkage. Production of TGF-beta1 accounted for the reciprocal regulation of IFN-gamma production by CTLA-4 engagement. Following CD4+ T cell activation, intracellular growth of Leishmania chagasi in cocultured splenic macrophages required both CTLA-4 function and TGF-beta1 secretion. Cross-linkage of CTLA-4 markedly increased L. chagasi replication in cocultures of infected macrophages and activated CD4+ T cells, and parasite growth could be completely blocked with neutralizing anti-TGF-beta1 Ab. Exogenous addition of rTGF-beta1 restored parasite growth in cultures protected from parasitism by CTLA-4 blockade. These results indicate that the negative costimulatory receptor CTLA-4 is critically involved in TGF-beta production and in intracellular parasite replication seen in murine kalaazar.
Details
- Title: Subtitle
- TGF-β Mediates CTLA-4 Suppression of Cellular Immunity in Murine Kalaazar
- Creators
- Nitza A GomesCerli R GattassVictor Barreto-de-SouzaMary E WilsonGeorge A DosReis
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.164(4), pp.2001-2008
- DOI
- 10.4049/jimmunol.164.4.2001
- PMID
- 10657651
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 02/15/2000
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984002374002771
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