title: Anti-IL-2 treatment impairs the expansion of T(reg) cell population during acute malaria and enhances the Th1 cell response at the chronic disease.
abstract: Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+) T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory T (T(reg)) cells has been implicated in both development of clinical immunity and parasite persistence. To evaluate whether IL-2 is required to induce and to sustain the suppressive activity of T(reg) cells in malaria, we examined in detail the effects of anti-IL-2 treatment with JES6-1 monoclonal antibody (mAb) on the splenic CD4(+) T cell response during acute and chronic P. chabaudi AS infection in C57BL/6 mice. JES6-1 treatment on days 0, 2 and 4 of infection partially inhibits the expansion of the CD4(+)CD25(+)Foxp3(+) cell population during acute malaria. Despite the concomitant secretion of IL-2 and expression of high affinity IL-2 receptor by large CD4(+) T cells, JES6-1 treatment does not impair effector CD4(+) T cell activation and IFN-γ production. However, at the chronic phase of the disease, an enhancement of cellular and humoral responses occurs in JES6-1-treated mice, with increased production of TNF-α and parasite-specific IgG2a antibodies. Furthermore, JES6-1 mAb completely blocked the in vitro proliferation of CD4(+) T cells from non-treated chronic mice, while it further increased the response of CD4(+) T cells from JES6-1-treated chronic mice. We conclude that JES6-1 treatment impairs the expansion of T(reg) cell population during early P. chabaudi malaria and enhances the Th1 cell response in the late phase of the disease.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brasil. cazago@usp.br
authors.forename: Cláudia A
authors.initials: CA
authors.lastname: Zago
authors.forename: Karina R
authors.initials: KR
authors.lastname: Bortoluci
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Sardinha
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Pretel
authors.forename: Sheyla I
authors.initials: SI
authors.lastname: Castillo-Méndez
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Freitas do Rosário
authors.forename: Meire I
authors.initials: MI
authors.lastname: Hiyane
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Muxel
authors.forename: Sérgio M
authors.initials: SM
authors.lastname: Rodriguez-Málaga
authors.forename: Ises A
authors.initials: IA
authors.lastname: Abrahamsohn
authors.forename: José M
authors.initials: JM
authors.lastname: Álvarez
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: D'Império Lima
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008288:Malaria / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508022:Il2rb protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D007371:Interferon-gamma