title: Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood.
abstract: γδ T cells expressing Vδ2 may be instrumental in the control of malaria, because they inhibit the replication of blood-stage parasites in vitro and expand during acute malaria infection. However, Vδ2 T-cell frequencies and function are lower among children with heavy prior malaria exposure. It remains unclear whether malaria itself is driving this loss. Here we measure Vδ2 T-cell frequency, cytokine production, and degranulation longitudinally in Ugandan children enrolled in a malaria chemoprevention trial from 6 to 36 months of age. We observed a progressive attenuation of the Vδ2 response only among children incurring high rates of malaria. Unresponsive Vδ2 T cells were marked by expression of CD16, which was elevated in the setting of high malaria transmission. Moreover, chemoprevention during early childhood prevented the development of dysfunctional Vδ2 T cells. These observations provide insight into the role of Vδ2 T cells in the immune response to chronic malaria.
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Lila A
authors.initials: LA
authors.lastname: Farrington
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Tara I
authors.initials: TI
authors.lastname: McIntyre
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Hilary M
authors.initials: HM
authors.lastname: Vance
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowen
authors.affiliation: Departments of Medicine, University of California San Francisco Center for Biomedical Research, The Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Boyle
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Felistas
authors.initials: F
authors.lastname: Nankya
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Samuel
authors.initials: S
authors.lastname: Wamala
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Ann
authors.initials: A
authors.lastname: Auma
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Mayimuna
authors.initials: M
authors.lastname: Nalubega
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Esther
authors.initials: E
authors.lastname: Sikyomu
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Kate
authors.initials: K
authors.lastname: Naluwu
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Victor
authors.initials: V
authors.lastname: Bigira
authors.affiliation: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: James
authors.initials: J
authors.lastname: Kapisi
authors.affiliation: Departments of Medicine, University of California San Francisco.
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Departments of Medicine, University of California San Francisco Pediatrics, University of California San Francisco.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
mesh_terms: D037621:Artemisinins / Q000008:administration & dosage; D002675:Child, Preschool; D004338:Drug Combinations; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D011739:Pyrimethamine / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D013413:Sulfadoxine / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*; D010879:Piperazines
chemical_list: D037621:Artemisinins; D004338:Drug Combinations; D058851:GPI-Linked Proteins; D011739:Pyrimethamine; D011804:Quinolines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D013413:Sulfadoxine; C428200:FCGR3B protein, human; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines
keywords: CD16; Plasmodium falciparum; immunologic tolerance; malaria; γδ T cells