Unresponsive CD4+ T lymphocytes from Leishmania chagasi-infected mice increase cytokine production and mediate parasite killing after blockade of B7-1/CTLA-4 molecular pathway

N A Gomes; V Barreto-de-Souza; M E Wilson; G A DosReis

doi:10.1086/314520

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Unresponsive CD4+ T lymphocytes from Leishmania chagasi-infected mice increase cytokine production and mediate parasite killing after blockade of B7-1/CTLA-4 molecular pathway

Journal article

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Peer reviewed

Unresponsive CD4+ T lymphocytes from Leishmania chagasi-infected mice increase cytokine production and mediate parasite killing after blockade of B7-1/CTLA-4 molecular pathway

N A Gomes, V Barreto-de-Souza, M E Wilson and G A DosReis

The Journal of infectious diseases, Vol.178(6), pp.1847-1851

12/1998

DOI: 10.1086/314520

PMID: 9815249

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Abstract

Infection of BALB/c mice with Leishmania chagasi results in progressive increase of parasite burden in spleen, in spite of extensive T cell activation in situ. Explanted splenic CD4+ T cells showed decreased proliferation to anti-CD3, compared with controls, and no response to L. chagasi recombinant antigen Lcr1. Blockade of the negative costimulatory receptor CTLA-4 restored responses to anti-CD3 and induced vigorous responses to Lcr1. Blockade of B7-1, but not B7-2, also enhanced T cell responsiveness. CTLA-4 blockade completely restored activation-induced interleukin-2 secretion and increased interferon-gamma production. The effect, however, was not restricted to Th1 responses, since CTLA-4 blockade also enhanced antigen-induced interleukin-4 secretion. CTLA-4 blockade induced almost complete elimination of parasite burden in splenocyte cultures activated with anti-CD3 or Lcr1. These results indicate that CTLA-4 engagement by B7-1 plays an important role in maintaining unresponsiveness in CD4+ T cells in this model of chronic visceral leishmaniasis.

Leishmaniasis - immunology

Cricetinae

Lymphocyte Activation

B7-1 Antigen - physiology

Th1 Cells - immunology

Antigens, Differentiation - physiology

CTLA-4 Antigen

Interleukin-4 - biosynthesis

Animals

Abatacept

Immunoconjugates

CD3 Complex - immunology

Mesocricetus

Female

T-Lymphocytes - immunology

Mice

Mice, Inbred BALB C

Interleukin-2 - biosynthesis

Chronic Disease

Cytokines - biosynthesis

Antigens, CD

Details

Title: Subtitle: Unresponsive CD4+ T lymphocytes from Leishmania chagasi-infected mice increase cytokine production and mediate parasite killing after blockade of B7-1/CTLA-4 molecular pathway
Creators: N A Gomes - Immunobiology Program, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Jameiro, Brazil
V Barreto-de-Souza
M E Wilson
G A DosReis
Resource Type: Journal article
Publication Details: The Journal of infectious diseases, Vol.178(6), pp.1847-1851
DOI: 10.1086/314520
PMID: 9815249
NLM abbreviation: J Infect Dis
ISSN: 0022-1899
eISSN: 1537-6613
Publisher: United States
Language: English
Date published: 12/1998
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984002385802771

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