SARS-CoV-2-specific T cell responses and immune regulation in infected pregnant women

• Published in: Journal of reproductive immunology Vol. 149; p. 103464
• Main Authors: Hsieh, Li-En, Grifoni, Alba, Dave, Hiral, Wang, Jasmine, Johnson, Diana, Zellner, Jennifer, Sidney, John, Chambers, Christina, Franco, Alessandra
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2022; The Authors. Published by Elsevier B.V
• Subjects: Adult; COVID-19 - immunology; Female; Humans; Immune regulation; Memory T Cells - immunology; Obstetrics and Gynecology; Placenta - immunology; Pregnancy; Pregnancy Complications, Infectious - immunology; Prospective Studies; Regulatory T cells; SARS-CoV-2; SARS-CoV-2 - immunology; T cells; T-Lymphocytes, Regulatory - immunology; Tolerogenic dendritic cells; cDC; MP; AIM; iTreg; Treg; Immune regulation; TEMRA; T cells; Regulatory T cells; tmDC; Tolerogenic dendritic cells; ILT-4; Pregnancy; SARS-CoV-2; Th; APC; SI; CTL; TEM; TCM; DC; activation-induced cell markers; severe acute respiratory syndrome coronavirus-2; stimulation index; effector memory T cells; megapool; immune regulation; classical DC; T CM; T EM; dendritic cells; T EMRA; cytotoxic T cells; terminally-differentiated effector T cells; tolerogenic myeloid DC; antigen-presenting cells; immunoglobulin-like transcript-4; pregnancy; tolerogenic dendritic cells; regulatory T cells; central memory T cells; peripherally-induced Treg; T helper cells
• ISSN: 0165-0378; 1872-7603; 1872-7603
• DOI: 10.1016/j.jri.2021.103464

•The SARS-CoV-2-specific T cell response in pregnancy is well developed.•Pre-existing inflammatory conditions do not affect the T cell response to SARS-CoV-2.•The innate compartment relevant for the immune regulation is normal.•Memory T cells were low close to delivery: tissue resident for neonatal protection? We studied the T cell response to SARS-CoV-2 spike and non-spike peptide epitopes in eight convalescent pregnant women together with the immune monitoring that included innate tolerogenic dendritic cell populations important to maintain the immunological mother/fetus interface to address a potential risk for the antiviral cellular response in the outcome of pregnancy. Four subjects had pre-existing chronic inflammatory conditions that could have potentially affected the SARS-CoV-2-specific T cell response. Seven of eight subjects responded to SARS-CoV-2 peptides with differences within CD4+ T helper (Th) and CD8+ cytotoxic T cells (CTL). SARS-CoV-2-specific inducible regulatory T cells (iTreg) were numerous in circulation. CD4+ T cell memory included central memory T cells (TCM) and effector memory (TEM). As far as the CD8+ memory repertoire, TCM and TEM were very low or absent in eight of eight subjects and only effector cells that revert to CD45RA+, defined as TEMRA were measurable in circulation. T cells were in the normal range in all subjects regardless of pre-existing inflammatory conditions. The immune phenotype indicated the expansion and activation of tolerogenic myeloid dendritic cells including CD14+ cDC2 and CD4+ ILT-4+ tmDC. In summary, SARS-CoV-2 infection induced a physiological anti-viral T cell response in pregnant women that included SARS-CoV-2-specific iTreg with no negative effects on the tolerogenic innate dendritic cell repertoire relevant to the immune homeostasis of the maternal-fetal interface. All eight subjects studied delivered full-term, healthy infants.