Systemic CD4 cytotoxic T cells improve protection against PRRSV-1 transplacental infection

Yanli Li; Ivan Díaz; Gerard Martín-Valls; Niklas Beyersdorf; Enric Mateu

doi:10.3389/fimmu.2022.1020227

Systemic CD4 cytotoxic T cells improve protection against PRRSV-1 transplacental infection

Front Immunol. 2023 Jan 17:13:1020227. doi: 10.3389/fimmu.2022.1020227. eCollection 2022.

Authors

Yanli Li¹, Ivan Díaz², Gerard Martín-Valls¹, Niklas Beyersdorf³, Enric Mateu¹

Affiliations

¹ Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain.
² Centre de Recerca en Sanitat Animal, Institut de Recerca en Tecnologies Agroalimentáries (IRTA-CReSA), Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain.
³ Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.

Abstract

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major swine pathogens causing reproductive failure in sows. Although modified-live virus (MLV) vaccines are available, only partial protection against heterologous strains is produced, thus vaccinated sows can be infected and cause transplacental infection. The immune effector mechanisms involved are largely unknown.

Methods: The present study investigated the role of cytotoxic lymphocytes, including cytotoxic T cells (CTL), NKT, and NK cells, from blood in preventing PRRSV-1 transplacental infection in vaccinated primiparous sows (two doses vaccinated). Sows from a PRRSV-1 unstable farm were bled just before the last month of gestation (critical period for transplacental infection), then followed to determine whether sows delivered PRRSV-1-infected (n=8) or healthy (n=10) piglets. After that, functions of CTL, NKT, and NK cells in the two groups of sows were compared.

Results: No difference was found through cell surface staining. But upon in vitro re-stimulation with the circulating field virus, sows that delivered healthy piglets displayed a higher frequency of virus-specific CD107a⁺ IFN-γ-producing T cells, which accumulated in the CD4⁺ compartment including CD4 single-positive (CD4 SP) and CD4/CD8α double-positive (CD4/CD8α DP) subsets. The same group of sows also harbored a higher proportion of CD107a⁺ TNF-α-producing T cells that predominantly accumulated in CD4/CD8α double-negative (CD4/CD8α DN) subset. Consistently, CD4 SP and CD4/CD8α DN T cells from sows delivering healthy piglets had a higher virus-specific proliferative response. Additionally, in sows that delivered PRRSV-1-infected piglets, a positive correlation of virus-specific IFN-γ response with average Ct values of umbilical cords of newborn piglets per litter was observed.

Conclusion: Our data strongly suggest that CTL responses correlate with protection against PRRSV-1 transplacental infection, being executed by CD4 T cells (IFN-γ related) and/or CD4/CD8α DN T cells (TNF-α related).

Keywords: CTL; NK; NKT; PRRSV-1; transplacental infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Female
Porcine Reproductive and Respiratory Syndrome* / prevention & control
Porcine respiratory and reproductive syndrome virus*
Swine
T-Lymphocytes, Cytotoxic
Tumor Necrosis Factor-alpha
Vaccines, Attenuated

Substances

Tumor Necrosis Factor-alpha
Antibodies, Viral
Vaccines, Attenuated

Grants and funding

This work was supported by the Boehringer Ingelheim European PRRS Research Award 2019 “Role of cytotoxic T lymphocytes in gilts after MLV vaccination in protection against vertical transmission of PRRSV” and the Veterinary Diagnostic Laboratory Service of Universitat Autònoma de Barcelona (UAB). Anti-CD28 antibody production was supported by SFB1525 Cardio-immune Interfaces (DFG 453989101)-project A2.