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: Lila A Farrington, Prasanna Jagannathan, Tara I McIntyre, Hilary M Vance, Katherine Bowen, Michelle J Boyle, Felistas Nankya, Samuel Wamala, Ann Auma, Mayimuna Nalubega, Esther Sikyomu, Kate Naluwu, Victor Bigira, James Kapisi, Grant Dorsey, Moses R Kamya, Margaret E Feeney
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 213 Issue 9 Pg. 1483-90 (May 01 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 26667315 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Artemisinins
• Drug Combinations
• FCGR3B protein, human
• GPI-Linked Proteins
• Quinolines
• Receptors, Antigen, T-Cell, gamma-delta
• Receptors, IgG
• fanasil, pyrimethamine drug combination
• artenimol
• Sulfadoxine
• piperaquine
• Pyrimethamine

Topics

• Artemisinins (administration & dosage)
• Child, Preschool
• Drug Combinations
• GPI-Linked Proteins (immunology)
• Humans
• Immune Tolerance
• Infant
• Longitudinal Studies
• Malaria, Falciparum (immunology, prevention & control)
• Plasmodium falciparum (immunology)
• Pyrimethamine (administration & dosage)
• Quinolines (administration & dosage)
• Receptors, Antigen, T-Cell, gamma-delta (immunology)
• Receptors, IgG (immunology)
• Sulfadoxine (administration & dosage)
• T-Lymphocyte Subsets (immunology)
• Up-Regulation (immunology)