biostudies-literatureCosta PAFundação de Amparo à Pesquisa do Estado de Minas GeraisNational Institute of Allergy and Infectious DiseasesIntramural NIH HHSNIAID NIH HHSNational Institute of Science and Technology for VaccinesNational Institutes of HealthNIHNIAIDConselho Nacional de Desenvolvimento Cientifico e Tecnologico1999-2010https://www.ebi.ac.uk/biostudies/studies/S-EPMC4655853biostudies-literatureUnknown212(12)The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4(+) and CD8(+) T cells. Higher frequencies of CD4(+) express more than 1 regulatory molecule compared to CD8(+) T cells. Moreover, lower proportions of CD4(+) T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin-3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function.The Journal of infectious diseasesInduction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.PMC4655853CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ 00077-09CBB-PPM-00426-13483098/2011-6R01 AI079293Pereira DBLeoratti FMCosta PATada MSSoares ISJunqueira CGazzinelli RTBarber DLFigueiredo MMAntonelli LRfalseInduction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4(+) and CD8(+) T cells. Higher frequencies of CD4(+) express more than 1 regulatory molecule compared to CD8(+) T cells. Moreover, lower proportions of CD4(+) T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin-3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function.2015-01-01T00:00:00Z2015 Dec2025-04-26T16:17:28.891Z2019-03-27T02:02:33ZS-EPMC46558532601928410.1093/infdis/jiv306