Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns

Abstract Introduction HIV‐exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV‐unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T‐cell receptor diversity, and activation...

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Main Authors: Yesenia Brito‐Pérez, Rodrigo T. Camacho‐Pacheco, Noemi Plazola‐Camacho, Diana Soriano‐Becerril, Irma A. Coronado‐Zarco, Gabriela Arreola‐Ramírez, Gabriela González‐Pérez, Alma Herrera‐Salazar, Julio Flores‐González, Mextli Y. Bermejo‐Haro, Brenda G. Casorla‐Cervantes, Ismael A. Soto‐López, Jessica Hernández‐Pineda, Claudia Sandoval‐Montes, Sandra Rodríguez‐Martínez, Ricardo Figueroa‐Damian, Ismael Mancilla‐Herrera
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.507
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author Yesenia Brito‐Pérez
Rodrigo T. Camacho‐Pacheco
Noemi Plazola‐Camacho
Diana Soriano‐Becerril
Irma A. Coronado‐Zarco
Gabriela Arreola‐Ramírez
Gabriela González‐Pérez
Alma Herrera‐Salazar
Julio Flores‐González
Mextli Y. Bermejo‐Haro
Brenda G. Casorla‐Cervantes
Ismael A. Soto‐López
Jessica Hernández‐Pineda
Claudia Sandoval‐Montes
Sandra Rodríguez‐Martínez
Ricardo Figueroa‐Damian
Ismael Mancilla‐Herrera
author_facet Yesenia Brito‐Pérez
Rodrigo T. Camacho‐Pacheco
Noemi Plazola‐Camacho
Diana Soriano‐Becerril
Irma A. Coronado‐Zarco
Gabriela Arreola‐Ramírez
Gabriela González‐Pérez
Alma Herrera‐Salazar
Julio Flores‐González
Mextli Y. Bermejo‐Haro
Brenda G. Casorla‐Cervantes
Ismael A. Soto‐López
Jessica Hernández‐Pineda
Claudia Sandoval‐Montes
Sandra Rodríguez‐Martínez
Ricardo Figueroa‐Damian
Ismael Mancilla‐Herrera
author_sort Yesenia Brito‐Pérez
collection DOAJ
description Abstract Introduction HIV‐exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV‐unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T‐cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4+ T cells. Method To characterize the Th cell profile, we evaluated the frequency of Th1 (CD183+CD194−CD196−/CXCR3+CCR4−CCR6−), Th2 (CD183−CD194+CD196−/CXCR3−CCR4+CCR6−), Th17 (CD183−CD194+CD196+/CXCR3−CCR4+CCR6+), and CD4+CD25++ blood T‐cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4+ T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4+ T cells to differentiate into interferon (IFN)‐γ‐producing Th1 CD4+ T cells in vitro. Results Lower percentages of differentiated Th1, Th2, Th17, and CD4+CD25++ T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)‐2 and IL‐4. Interestingly, under Th1 differentiation conditions, the percentages of CD4+IFN‐γ+ T cells and soluble IFN‐γ were higher in HEU newborns than in HUU newborns. Conclusion HEU neonates are born with reduced proportions of differentiated Th1/Th2/Th17 and CD4+CD25++ T cells, but the intrinsic abilities of CD4+ T cells to acquire a Th1 profile are not affected by the adverse maternal milieu during development.
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spelling doaj.art-08b8026913fc4464bf52d9b69d5fc5c22022-12-21T17:34:21ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941541155310.1002/iid3.507Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newbornsYesenia Brito‐Pérez0Rodrigo T. Camacho‐Pacheco1Noemi Plazola‐Camacho2Diana Soriano‐Becerril3Irma A. Coronado‐Zarco4Gabriela Arreola‐Ramírez5Gabriela González‐Pérez6Alma Herrera‐Salazar7Julio Flores‐González8Mextli Y. Bermejo‐Haro9Brenda G. Casorla‐Cervantes10Ismael A. Soto‐López11Jessica Hernández‐Pineda12Claudia Sandoval‐Montes13Sandra Rodríguez‐Martínez14Ricardo Figueroa‐Damian15Ismael Mancilla‐Herrera16Infectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoNeonatology Department National Institute of Perinatology (INPer) Mexico City MexicoNeonatology Department National Institute of Perinatology (INPer) Mexico City MexicoDepartment of Physiology and Cellular Development National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoDepartamento de Inmunología, Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional Ciudad de México MéxicoDepartamento de Inmunología, Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional Ciudad de México MéxicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoInfectology and Immunology Department National Institute of Perinatology (INPer) Mexico City MexicoAbstract Introduction HIV‐exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV‐unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T‐cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4+ T cells. Method To characterize the Th cell profile, we evaluated the frequency of Th1 (CD183+CD194−CD196−/CXCR3+CCR4−CCR6−), Th2 (CD183−CD194+CD196−/CXCR3−CCR4+CCR6−), Th17 (CD183−CD194+CD196+/CXCR3−CCR4+CCR6+), and CD4+CD25++ blood T‐cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4+ T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4+ T cells to differentiate into interferon (IFN)‐γ‐producing Th1 CD4+ T cells in vitro. Results Lower percentages of differentiated Th1, Th2, Th17, and CD4+CD25++ T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)‐2 and IL‐4. Interestingly, under Th1 differentiation conditions, the percentages of CD4+IFN‐γ+ T cells and soluble IFN‐γ were higher in HEU newborns than in HUU newborns. Conclusion HEU neonates are born with reduced proportions of differentiated Th1/Th2/Th17 and CD4+CD25++ T cells, but the intrinsic abilities of CD4+ T cells to acquire a Th1 profile are not affected by the adverse maternal milieu during development.https://doi.org/10.1002/iid3.507HIV‐exposed uninfected newbornsTh cellsTh1/Th2/Th17/Treg/CD4+CD25++ T cells and Th1 differentiation
spellingShingle Yesenia Brito‐Pérez
Rodrigo T. Camacho‐Pacheco
Noemi Plazola‐Camacho
Diana Soriano‐Becerril
Irma A. Coronado‐Zarco
Gabriela Arreola‐Ramírez
Gabriela González‐Pérez
Alma Herrera‐Salazar
Julio Flores‐González
Mextli Y. Bermejo‐Haro
Brenda G. Casorla‐Cervantes
Ismael A. Soto‐López
Jessica Hernández‐Pineda
Claudia Sandoval‐Montes
Sandra Rodríguez‐Martínez
Ricardo Figueroa‐Damian
Ismael Mancilla‐Herrera
Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
Immunity, Inflammation and Disease
HIV‐exposed uninfected newborns
Th cells
Th1/Th2/Th17/Treg/CD4+CD25++ T cells and Th1 differentiation
title Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
title_full Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
title_fullStr Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
title_full_unstemmed Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
title_short Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns
title_sort impaired t helper cell responses in human immunodeficiency virus exposed uninfected newborns
topic HIV‐exposed uninfected newborns
Th cells
Th1/Th2/Th17/Treg/CD4+CD25++ T cells and Th1 differentiation
url https://doi.org/10.1002/iid3.507
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