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Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection.
J Immunol 2012; 188(11):5467-77JI

Abstract

It is well established that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play a crucial role in the course of different infectious diseases. However, contradictory results have been published regarding to malaria infection. In this study, we report that specific ablation of Foxp3(+) Tregs in Plasmodium yoelii-infected DEREG-BALB/c mice leads to an increase in T cell activation accompanied by a significant decrease in parasitemia. To better understand how Foxp3(+) Tregs orchestrate this phenotype, we used microarrays to analyze CD4(+)CD25(+)Foxp3(+) Tregs and CD4(+)CD25(-)Foxp3(-) T cells in the course of P. yoelii infection. Using this approach we identified genes specifically upregulated in CD4(+)CD25(+)Foxp3(+) Tregs in the course of infection, such as G-protein-coupled receptor 83 and Socs2. This analysis also revealed that both CD4(+)CD25(+)Foxp3(+) Tregs and CD4(+)CD25(-)Foxp3(-) T cells upregulate CTLA-4, granzyme B, and, more strikingly, IL-10 during acute blood infection. Therefore, we aimed to define the function of T cell-derived IL-10 in this context by Cre/loxP-mediated selective conditional inactivation of the IL-10 gene in T cells. Unexpectedly, IL-10 ablation in T cells exerts only a minor effect on parasite clearance, even though CD8(+) T cells are more strongly activated, the production of IFN-γ and TNF-α by CD4(+)CD25(-) T cells is increased, and the suppressive activity of CD4(+)CD25(+) Tregs is reduced upon infection. In summary, these results suggest that CD4(+)Foxp3(+) Tregs modulate the course of P. yoelii infection in BALB/c mice. Moreover, CD4(+) T cell-derived IL-10 affects T effector function and Treg activity, but has only a limited direct effect on parasite clearance in this model.

Authors+Show Affiliations

Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22544931

Citation

Abel, Simone, et al. "Strong Impact of CD4+ Foxp3+ Regulatory T Cells and Limited Effect of T Cell-derived IL-10 On Pathogen Clearance During Plasmodium Yoelii Infection." Journal of Immunology (Baltimore, Md. : 1950), vol. 188, no. 11, 2012, pp. 5467-77.
Abel S, Lückheide N, Westendorf AM, et al. Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection. J Immunol. 2012;188(11):5467-77.
Abel, S., Lückheide, N., Westendorf, A. M., Geffers, R., Roers, A., Müller, W., ... Hansen, W. (2012). Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection. Journal of Immunology (Baltimore, Md. : 1950), 188(11), pp. 5467-77. doi:10.4049/jimmunol.1102223.
Abel S, et al. Strong Impact of CD4+ Foxp3+ Regulatory T Cells and Limited Effect of T Cell-derived IL-10 On Pathogen Clearance During Plasmodium Yoelii Infection. J Immunol. 2012 Jun 1;188(11):5467-77. PubMed PMID: 22544931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection. AU - Abel,Simone, AU - Lückheide,Nadja, AU - Westendorf,Astrid M, AU - Geffers,Robert, AU - Roers,Axel, AU - Müller,Werner, AU - Sparwasser,Tim, AU - Matuschewski,Kai, AU - Buer,Jan, AU - Hansen,Wiebke, Y1 - 2012/04/27/ PY - 2012/5/1/entrez PY - 2012/5/1/pubmed PY - 2012/8/15/medline SP - 5467 EP - 77 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 188 IS - 11 N2 - It is well established that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play a crucial role in the course of different infectious diseases. However, contradictory results have been published regarding to malaria infection. In this study, we report that specific ablation of Foxp3(+) Tregs in Plasmodium yoelii-infected DEREG-BALB/c mice leads to an increase in T cell activation accompanied by a significant decrease in parasitemia. To better understand how Foxp3(+) Tregs orchestrate this phenotype, we used microarrays to analyze CD4(+)CD25(+)Foxp3(+) Tregs and CD4(+)CD25(-)Foxp3(-) T cells in the course of P. yoelii infection. Using this approach we identified genes specifically upregulated in CD4(+)CD25(+)Foxp3(+) Tregs in the course of infection, such as G-protein-coupled receptor 83 and Socs2. This analysis also revealed that both CD4(+)CD25(+)Foxp3(+) Tregs and CD4(+)CD25(-)Foxp3(-) T cells upregulate CTLA-4, granzyme B, and, more strikingly, IL-10 during acute blood infection. Therefore, we aimed to define the function of T cell-derived IL-10 in this context by Cre/loxP-mediated selective conditional inactivation of the IL-10 gene in T cells. Unexpectedly, IL-10 ablation in T cells exerts only a minor effect on parasite clearance, even though CD8(+) T cells are more strongly activated, the production of IFN-γ and TNF-α by CD4(+)CD25(-) T cells is increased, and the suppressive activity of CD4(+)CD25(+) Tregs is reduced upon infection. In summary, these results suggest that CD4(+)Foxp3(+) Tregs modulate the course of P. yoelii infection in BALB/c mice. Moreover, CD4(+) T cell-derived IL-10 affects T effector function and Treg activity, but has only a limited direct effect on parasite clearance in this model. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/22544931/Strong_impact_of_CD4+_Foxp3+_regulatory_T_cells_and_limited_effect_of_T_cell_derived_IL_10_on_pathogen_clearance_during_Plasmodium_yoelii_infection_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=22544931 DB - PRIME DP - Unbound Medicine ER -