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Virulence of Toxoplasma gondii is associated with distinct dendritic cell responses and reduced numbers of activated CD8+ T cells.
Title | Virulence of Toxoplasma gondii is associated with distinct dendritic cell responses and reduced numbers of activated CD8+ T cells. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Tait, ED, Jordan, KA, Dupont, CD, Harris, TH, Gregg, B, Wilson, EH, Pepper, M, Dzierszinski, F, Roos, DS, Hunter, CA |
Journal | J Immunol |
Volume | 185 |
Issue | 3 |
Pagination | 1502-12 |
Date Published | 2010 Aug 1 |
ISSN | 1550-6606 |
Keywords | Animals, CD8-Positive T-Lymphocytes, Cell Proliferation, Cells, Cultured, Dendritic Cells, Epitopes, T-Lymphocyte, Female, Lymphocyte Activation, Lymphocyte Count, Lymphopenia, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Toxoplasma, Toxoplasmosis, Animal, Virulence |
Abstract | The Toxoplasma gondii population consists of multiple strains, defined by genotype and virulence. Previous studies have established that protective immunity to this organism is mediated by IL-12, which drives T cells to produce IFN-gamma. Paradoxically, although type I and type II strains of T. gondii both induce IL-12 and IFN-gamma in the mouse, type I parasites are lethal, whereas type II strains establish chronic infection. The cellular basis for these strain-dependent differences remains unclear. To better understand these events, the CD8(+) T cell and dendritic cell (DC) responses to transgenic, OVA-expressing type I RH (RH OVA) and type II Prugniuad (Pru OVA) parasites were examined. Pru OVA-infected mice developed a robust DC response at the site of infection and the draining lymph node and generated a population of endogenous OVA-specific CD8(+) T cells. In contrast, RH OVA-infected mice had fewer DCs and OVA-specific CD8(+) T cells. RH OVA-infected mice given preactivated OVA-specific CD8(+) T cells were protected, suggesting that reduced DC-derived signals contributed to the low OVA-specific CD8(+) T cell numbers observed during type I infection. Indeed, DC depletion prior to Pru OVA infection resulted in a failure to generate activated OVA-specific CD8(+) T cells, and IL-12p70 treatment during RH OVA infection modestly increased the number of Ag-specific cells. Together, these data are consistent with a model of immunity to T. gondii in which strain-dependent DC responses shape the generation of Ag-specific CD8(+) T cells and determine the outcome of infection. |
DOI | 10.4049/jimmunol.0903450 |
Alternate Journal | J. Immunol. |
PubMed ID | 20592284 |
PubMed Central ID | PMC3039871 |
Grant List | R01 AI041158 / AI / NIAID NIH HHS / United States R01 AI042334 / AI / NIAID NIH HHS / United States R01 AI042334-12 / AI / NIAID NIH HHS / United States T32 AI007532 / AI / NIAID NIH HHS / United States T32 AI007532-12 / AI / NIAID NIH HHS / United States T32 AI007532-14 / AI / NIAID NIH HHS / United States |