Cord Blood Vγ2Vδ2 T Cells Provide a Molecular Marker for the Influence of Pregnancy-Associated Malaria on Neonatal Immunity

• Published in: The Journal of infectious diseases 2014-05, Vol.209 (10), p.1653-1662
• Main Authors: Cairo, Cristiana, Longinaker, Nyaradzo, Cappelli, Giulia, Leke, Rose G. F., Ondo, Manuel Mve, Djokam, Rosine, Fogako, Josephine, Leke, Robert J., Sagnia, Bertrand, Sosso, Samuel, Colizzi, Vittorio, Pauza, C. David
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers; Blood; Cord blood; Female; Fetal Blood - cytology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - immunology; HIV infections; Human protozoal diseases; Humans; Immunity, Maternally-Acquired; Immunoglobulin gamma-Chains - genetics; Immunoglobulin gamma-Chains - metabolism; Infant, Newborn; Infections; Infectious diseases; Lymphocytes; Major and Brief Reports; Malaria; Malaria, Falciparum - immunology; Medical sciences; Microbiology; Newborns; PARASITES; Parasitic diseases; Phenotypes; Pregnancy; Pregnancy Complications, Parasitic - immunology; Protozoal diseases; T lymphocytes; T-Lymphocyte Subsets - physiology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit802

Background. Plasmodium falciparum placental infection primes the fetal immune system and alters infant immunity. Mechanisms leading to these outcomes are not completely understood. We focused on Vγ2Vδ2 cells, which are part of the immune response against many pathogens, including P. falciparum. These unconventional lymphocytes respond directly to small, nonpeptidic antigens, independent of major histocompatibility complex presentation. We wondered whether placental malaria, which may increase fetal exposure to P. falciparum metabolites, triggers a response by neonatal Vγ2Vδ2 lymphocytes that can be a marker for the extent of fetal exposure to malarial antigens. Methods. Cord blood mononuclear cells were collected from 15 neonates born to mothers with P. falciparum infection during pregnancy (8 with placental malaria) and 25 unexposed neonates. Vγ2Vδ2 cell phenotype, repertoire, and proliferative responses were compared between newborns exposed and those unexposed to P. falciparum. Results. Placental malaria-exposed neonates had increased proportions of central memory Vγ2Vδ2 cells in cord blood, with an altered Vγ2 chain repertoire ex vivo and after stimulation. Conclusion. Our results suggest that placental malaria affects the phenotype and repertoire of neonatal Vγ2Vδ2 lymphocytes. Placental malaria may lower the capacity for subsequent Vγ2Vδ2 cell responses and impair the natural resistance to infectious diseases or the response to pediatric vaccination.