{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Costa PA"],"funding":["Fundação de Amparo à Pesquisa do Estado de Minas Gerais","National Institute of Allergy and Infectious Diseases","Intramural NIH HHS","NIAID NIH HHS","National Institute of Science and Technology for Vaccines","National Institutes of Health","NIH","NIAID","Conselho Nacional de Desenvolvimento Cientifico e Tecnologico"],"pagination":["1999-2010"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4655853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["212(12)"],"pubmed_abstract":["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."],"journal":["The Journal of infectious diseases"],"pubmed_title":["Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production."],"pmcid":["PMC4655853"],"funding_grant_id":["CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ 00077-09","CBB-PPM-00426-13","483098/2011-6","R01 AI079293"],"pubmed_authors":["Pereira DB","Leoratti FM","Costa PA","Tada MS","Soares IS","Junqueira C","Gazzinelli RT","Barber DL","Figueiredo MM","Antonelli LR"],"additional_accession":[]},"is_claimable":false,"name":"Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.","description":"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.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Dec","modification":"2025-04-26T16:17:28.891Z","creation":"2019-03-27T02:02:33Z"},"accession":"S-EPMC4655853","cross_references":{"pubmed":["26019284"],"doi":["10.1093/infdis/jiv306"]}}