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CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.
- Source :
-
PLoS pathogens [PLoS Pathog] 2010 Dec 09; Vol. 6 (12), pp. e1001221. Date of Electronic Publication: 2010 Dec 09. - Publication Year :
- 2010
-
Abstract
- Studies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not improve parasite control or disease outcome. In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease. This protection was entirely dependent upon Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain. Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA-4 but not IL-10. These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes parasitology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes parasitology
CTLA-4 Antigen
Cell Proliferation
Forkhead Transcription Factors
Interleukin-10
Malaria, Cerebral prevention & control
Mice
Mice, Inbred C57BL
Plasmodium berghei
Antigens, CD pharmacology
Malaria, Cerebral immunology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory parasitology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 6
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 21170302
- Full Text :
- https://doi.org/10.1371/journal.ppat.1001221