TY - JOUR
T1 - Impaired T helper cell responses in human immunodeficiency virus-exposed uninfected newborns
AU - Brito-Pérez, Yesenia
AU - Camacho-Pacheco, Rodrigo T.
AU - Plazola-Camacho, Noemi
AU - Soriano-Becerril, Diana
AU - Coronado-Zarco, Irma A.
AU - Arreola-Ramírez, Gabriela
AU - González-Pérez, Gabriela
AU - Herrera-Salazar, Alma
AU - Flores-González, Julio
AU - Bermejo-Haro, Mextli Y.
AU - Casorla-Cervantes, Brenda G.
AU - Soto-López, Ismael A.
AU - Hernández-Pineda, Jessica
AU - Sandoval-Montes, Claudia
AU - Rodríguez-Martínez, Sandra
AU - Figueroa-Damian, Ricardo
AU - Mancilla-Herrera, Ismael
N1 - Publisher Copyright:
© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - HIV-exposed uninfected newborns
KW - Th cells
KW - Th/Th/Th/Treg/CD4CD25 T cells and Th differentiation
UR - http://www.scopus.com/inward/record.url?scp=85112764871&partnerID=8YFLogxK
U2 - 10.1002/iid3.507
DO - 10.1002/iid3.507
M3 - Artículo
C2 - 34409752
AN - SCOPUS:85112764871
SN - 2050-4527
VL - 9
SP - 1541
EP - 1553
JO - Immunity Inflammation and Disease
JF - Immunity Inflammation and Disease
IS - 4
ER -