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IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection.
J Immunol 2011; 186(8):4862-71JI

Abstract

To investigate the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in blood-stage malaria, we compared Plasmodium chabaudi AS infection in wild-type (WT) C57BL/6 and transgenic mice overexpressing the transcription factor Foxp3 (Foxp3Tg) and observed that Foxp3Tg mice experienced lethal infection and deficient malaria-specific immune responses. Adoptive transfer of total CD4(+) T cells from Foxp3Tg mice or CD4(+)CD25(+) T cells from WT mice to naive WT recipients confirmed that high numbers of Treg cells compromised immune control of malaria. Transfer of GFP(+)CD4(+)CD25(+) T cells to naive WT recipients together with immunohistochemical staining of spleens from infected WT mice demonstrated that Foxp3(+) Treg cells localized in the T cell area of the spleen. Determination of CD4(+)Foxp3(+) Treg cell responses in the spleen of infected WT mice revealed a significant but transient increase in CD4(+)Foxp3(+) Treg cells early in infection. This was followed by a significant and sustained decrease due to reduced proliferation and apoptosis of CD4(+)Foxp3(+) Treg cells. Importantly, the kinetics of IL-2 secretion by effector CD4(+)Foxp3(-) T cells coincided with changes in CD4(+)Foxp3(+) cells and the differentiation of CD4(+)T-bet(+)IFN-γ(+) cells required for immune control of infection. Administration of the IL-2/anti-IL-2 mAb (clone JES6-1) complex to infected WT mice increased the severity of P. chabaudi AS infection and promoted expansion of Foxp3(+) Treg cells. Collectively, these data demonstrate that the ability to control and eliminate P. chabaudi AS infection is due to a tight balance between natural Treg cells and effector CD4(+) Th1 cells, a balance regulated in part by IL-2.

Authors+Show Affiliations

Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, H3G 1A4 Canada.No 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

21389253

Citation

Berretta, Floriana, et al. "IL-2 Contributes to Maintaining a Balance Between CD4+Foxp3+ Regulatory T Cells and Effector CD4+ T Cells Required for Immune Control of Blood-stage Malaria Infection." Journal of Immunology (Baltimore, Md. : 1950), vol. 186, no. 8, 2011, pp. 4862-71.
Berretta F, St-Pierre J, Piccirillo CA, et al. IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection. J Immunol. 2011;186(8):4862-71.
Berretta, F., St-Pierre, J., Piccirillo, C. A., & Stevenson, M. M. (2011). IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection. Journal of Immunology (Baltimore, Md. : 1950), 186(8), pp. 4862-71. doi:10.4049/jimmunol.1003777.
Berretta F, et al. IL-2 Contributes to Maintaining a Balance Between CD4+Foxp3+ Regulatory T Cells and Effector CD4+ T Cells Required for Immune Control of Blood-stage Malaria Infection. J Immunol. 2011 Apr 15;186(8):4862-71. PubMed PMID: 21389253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection. AU - Berretta,Floriana, AU - St-Pierre,Jessica, AU - Piccirillo,Ciriaco A, AU - Stevenson,Mary M, Y1 - 2011/03/09/ PY - 2011/3/11/entrez PY - 2011/3/11/pubmed PY - 2011/8/2/medline SP - 4862 EP - 71 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 186 IS - 8 N2 - To investigate the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in blood-stage malaria, we compared Plasmodium chabaudi AS infection in wild-type (WT) C57BL/6 and transgenic mice overexpressing the transcription factor Foxp3 (Foxp3Tg) and observed that Foxp3Tg mice experienced lethal infection and deficient malaria-specific immune responses. Adoptive transfer of total CD4(+) T cells from Foxp3Tg mice or CD4(+)CD25(+) T cells from WT mice to naive WT recipients confirmed that high numbers of Treg cells compromised immune control of malaria. Transfer of GFP(+)CD4(+)CD25(+) T cells to naive WT recipients together with immunohistochemical staining of spleens from infected WT mice demonstrated that Foxp3(+) Treg cells localized in the T cell area of the spleen. Determination of CD4(+)Foxp3(+) Treg cell responses in the spleen of infected WT mice revealed a significant but transient increase in CD4(+)Foxp3(+) Treg cells early in infection. This was followed by a significant and sustained decrease due to reduced proliferation and apoptosis of CD4(+)Foxp3(+) Treg cells. Importantly, the kinetics of IL-2 secretion by effector CD4(+)Foxp3(-) T cells coincided with changes in CD4(+)Foxp3(+) cells and the differentiation of CD4(+)T-bet(+)IFN-γ(+) cells required for immune control of infection. Administration of the IL-2/anti-IL-2 mAb (clone JES6-1) complex to infected WT mice increased the severity of P. chabaudi AS infection and promoted expansion of Foxp3(+) Treg cells. Collectively, these data demonstrate that the ability to control and eliminate P. chabaudi AS infection is due to a tight balance between natural Treg cells and effector CD4(+) Th1 cells, a balance regulated in part by IL-2. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/21389253/IL_2_contributes_to_maintaining_a_balance_between_CD4+Foxp3+_regulatory_T_cells_and_effector_CD4+_T_cells_required_for_immune_control_of_blood_stage_malaria_infection_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21389253 DB - PRIME DP - Unbound Medicine ER -