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J Infect Dis. 2016 May 1;213(9):1483-90. doi: 10.1093/infdis/jiv600. Epub 2015 Dec 13.

Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood.

Author information

1
Departments of Medicine, University of California San Francisco.
2
Departments of Medicine, University of California San Francisco Center for Biomedical Research, The Burnet Institute, Melbourne, Victoria, Australia.
3
Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
4
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
5
Departments of Medicine, University of California San Francisco Pediatrics, University of California San Francisco.

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.

KEYWORDS:

CD16; Plasmodium falciparum; immunologic tolerance; malaria; γδ T cells

PMID:
26667315
PMCID:
PMC4813738
DOI:
10.1093/infdis/jiv600
[Indexed for MEDLINE]
Free PMC Article

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