Open AccessInduction of Inhibitory Receptors on T Cells DuringPlasmodium vivaxMalaria Impairs Cytokine Production
Author(s) -
Pedro Augusto Carvalho Costa,
Fabiana M. S. Leoratti,
María Marta Figueiredo,
Mauro Shugiro Tada,
Dhélio Batista Pereira,
Caroline Junqueira,
Irene da Silva Soares,
Daniel L. Barber,
Ricardo T. Gazzinelli,
Lis Ribeiro do Valle Antonelli
Publication year - 2015
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jiv306
Subject(s) - biology , cytotoxic t cell , immune system , plasmodium vivax , immunology , cd8 , effector , t cell , cytokine , il 2 receptor , microbiology and biotechnology , interleukin 21 , plasmodium falciparum , malaria , in vitro , biochemistry
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.