Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 12, Pages 3529-3541Publisher
WILEY
DOI: 10.1002/eji.201141507
Keywords
IL-2; IL-10; Immunosuppression; Treg cells; Toxoplasma gondii
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Funding
- PAPIIT (DGAPA, UNAM, Mexico) [IN-200608, IN-209111]
- CONACYT (Mexico) [79775, 102399, 102984]
- CONACYT [Registro 199991]
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Acute Toxoplasma gondii infection comprises an immunosuppression stage, characterized by a reduction in T-cell proliferation in vitro. Treg cells maintain the homeostasis of the immune system, but their role in T. gondii-induced suppression has not been addressed. We show herein that immunosuppression, affecting both CD4(+) and CD8(+) T-cell proliferation, concurs with a reduction in Treg-cell number. The residual Treg cells, however, are activated and display an increased suppressive capacity. We show that selective elimination of Treg cells using Foxp3(EGFP) mice leads to a full recovery of CD4(+) and CD8(+) T-cell proliferation. After Treg-cell removal, a reduced production of IL-10 was observed, but IL-2 levels were unchanged. The numbers of IL-10-producing Treg cells also increased during infection, although the in vitro neutralization of this cytokine did not modify T-cell proliferation, suggesting that IL-10 does not mediate the Treg-mediated suppression. However, addition of rIL-2 in vitro fully restored T-cell proliferation from infected animals. Thus, we show that Treg cells mediate the T-cell suppression observed during acute T. gondii infection through an IL-2-dependent mechanism. Our results provide novel insights into the regulation of the immune response against T. gondii.
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