SARS-CoV-2-specific T cell responses and immune regulation in infected pregnant women Journal of Reproductive Immunology

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 (T CM ) and effector memory (T EM ). As far as the CD8 + memory repertoire, T CM and T EM were very low or absent in eight of eight subjects and only effector cells that revert to CD45RA + , defined as T EMRA 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 acti- vation 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. DC leads to the polarization of T cell lineages

[1]  J. Sidney,et al.  Characterization of SARS‐CoV‐2 and common cold coronavirus‐specific T‐cell responses in MIS‐C and Kawasaki disease children , 2021, European journal of immunology.

[2]  S. Mallal,et al.  Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases , 2021, Cell Reports Medicine.

[3]  S. Mallal,et al.  Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases , 2020, bioRxiv.

[4]  E. Olsen,et al.  Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–October 3, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[5]  E. Olsen,et al.  Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy — SET-NET, 16 Jurisdictions, March 29–October 14, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[6]  M. Kikkert,et al.  Detailed immune monitoring of a pregnant woman with critical Covid-19 , 2020, Journal of Reproductive Immunology.

[7]  M. Lipsitch,et al.  Cross-reactive memory T cells and herd immunity to SARS-CoV-2 , 2020, Nature Reviews Immunology.

[8]  S. McLafferty,et al.  Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 — COVID-NET, 13 States, March 1–August 22, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[9]  J. Greenbaum,et al.  Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity , 2020, Cell.

[10]  S. Mallal,et al.  Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans , 2020, Science.

[11]  A. Sette,et al.  Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome , 2020, Science Immunology.

[12]  S. Gilboa,et al.  Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[13]  S. Farhadian,et al.  SARS-CoV-2 infection of the placenta. , 2020, The Journal of clinical investigation.

[14]  J. Greenbaum,et al.  Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals , 2020, Cell.

[15]  A. Benachi,et al.  Transplacental transmission of SARS-CoV-2 infection , 2020, Nature Communications.

[16]  Xiaobao Ying SARS-CoV-2 Infection , 2020 .

[17]  A. Franco Immune Regulation is the Most Relevant Arm of the Immune Response in Infants and Young Children. , 2020, Critical reviews in immunology.

[18]  R. Xu,et al.  Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study , 2019, PloS one.

[19]  C. Chambers,et al.  Approach to evaluating pregnancy safety of anti-rheumatic medications in the OTIS MotherToBaby pregnancy studies: what have we learned? , 2018, Rheumatology.

[20]  C. Chambers,et al.  Autoimmune conditions and comorbid depression in pregnancy: examining the risk of preterm birth and preeclampsia , 2017, Journal of Perinatology.

[21]  R. Rizzo,et al.  HLA-G expression levels influence the tolerogenic activity of human DC-10 , 2015, Haematologica.

[22]  P. Panina-Bordignon,et al.  HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche , 2015, Front. Immunol..

[23]  J. Kanegaye,et al.  Immune‐monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin , 2013, Clinical and experimental immunology.

[24]  A. Mitchell,et al.  Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants. , 2013, Vaccine.

[25]  M. Roncarolo,et al.  HLA-G expressing DC-10 and CD4+ T cells accumulate in human decidua during pregnancy , 2013, Human immunology.

[26]  Adrian Erlebacher,et al.  Immunology of the maternal-fetal interface. , 2013, Annual review of immunology.

[27]  Jeff E. Mold,et al.  Immunological tolerance during fetal development: from mouse to man. , 2012, Advances in immunology.

[28]  E. Hauben,et al.  Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. , 2010, Blood.

[29]  R. Xu,et al.  Birth outcomes in women who have taken leflunomide during pregnancy. , 2010, Arthritis and rheumatism.

[30]  Shimon Sakaguchi,et al.  Regulatory T cells exert checks and balances on self tolerance and autoimmunity , 2010, Nature Immunology.

[31]  M. Battaglia,et al.  Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans , 2007, Nature Reviews Immunology.

[32]  K. Red-Horse,et al.  Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. , 2004, The Journal of clinical investigation.

[33]  R. K. Miller,et al.  Postmarketing surveillance for human teratogenicity: a model approach. , 2001, Teratology.

[34]  S. Voß,et al.  Postmarketing surveillance , 1994, BMJ.