Brief Research Report: Expression of PD-1 and CTLA-4 in T Lymphocytes and Their Relationship With the Periparturient Period and the Endometrial Cytology of Dairy Cows During the Postpartum Period

Carolina Menezes Suassuna de Souza; Ewerton de Souza Lima; Raphael Ferreira Ordonho; Bianca Rafaella Rodrigues Dos Santos Oliveira; Rebeca Cordeiro Rodrigues; Marquiliano Farias de Moura; Daniel Magalhães Lima; Maiara Garcia Blagitz; Eduardo Milton Ramos Sanchez; Isac Almeida de Medeiros; Fernando Nogueira Souza; Artur Cezar de Carvalho Fernandes

doi:10.3389/fvets.2022.928521

Brief Research Report: Expression of PD-1 and CTLA-4 in T Lymphocytes and Their Relationship With the Periparturient Period and the Endometrial Cytology of Dairy Cows During the Postpartum Period

Front Vet Sci. 2022 Jul 22:9:928521. doi: 10.3389/fvets.2022.928521. eCollection 2022.

Authors

Carolina Menezes Suassuna de Souza^{1

2}, Ewerton de Souza Lima^{1

2}, Raphael Ferreira Ordonho^{1

2}, Bianca Rafaella Rodrigues Dos Santos Oliveira², Rebeca Cordeiro Rodrigues², Marquiliano Farias de Moura³, Daniel Magalhães Lima⁴, Maiara Garcia Blagitz^{5

6}, Eduardo Milton Ramos Sanchez^{1

7

8}, Isac Almeida de Medeiros⁹, Fernando Nogueira Souza^{1

2

6}, Artur Cezar de Carvalho Fernandes^{1

2}

Affiliations

¹ Programa de Pós-Graduação em Ciência Animal, Centro de Ciências Agrárias, Universidade Federal da Paraíba, Areia, Brazil.
² Núcleo Aplicado à Produção e Sanidade da Glândula Mamária (NAPROSA), Departamento de Ciências Veterinárias, Centro de Ciências Agrárias, Universidade Federal da Paraíba, Areia, Brazil.
³ Departamento de Ciências Veterinárias, Centro de Ciências Agrárias, Universidade Federal da Paraíba, Areia, Brazil.
⁴ Departamento de Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil.
⁵ Programa de Pós-Graduação em Saúde, Bem-Estar e Produção Animal Sustentável na Fronteira Sul, Universidade Federal da Fronteira Sul, Realeza, Brazil.
⁶ Veterinary Clinical Immunology Research Group, Departamento de Clínica Médica, Faculdade de Medicina Veterinária e Zootecnia, Universidade de S3ão Paulo, São Paulo, Brazil.
⁷ Department of Public Health, School of Health Sciences, National University Toribio Rodriguez de Mendoza of Amazonas, Chachapoyas, Peru.
⁸ Laboratório de Sorologia e Imunobiologia, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.
⁹ Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil.

Abstract

The present study sought to evaluate the expression of PD-1 and CTLA-4 in blood T lymphocytes during the periparturient period and their relationship with uterine health in dairy cows, as determined by endometrial cytology and serum concentrations of β-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs), which are indicators of a negative energy balance. The second objective of this study was to investigate whether the expression of PD-1 and CTLA-4 in T lymphocytes is associated with the serum acute phase-protein haptoglobin concentration during the periparturient period. To address these objectives, 26 clinically healthy dairy cows were used. Peripheral blood was collected 14 days prepartum (T-14), at calving (T0), and 30 days postpartum (T30) to measure the expression of PD-1 and CTLA-4 in blood T lymphocytes by flow cytometry. In addition, we collected blood at T0, 10 days after parturition (T10), and T30 to obtain serum and determine the serum concentrations of NEFA, BHB, and Hp. Endometrial cytology was performed at T10, 20 days after parturition (T20), and T30. In the present study, we observed higher expression of CTLA-4 and PD-1 in T lymphocytes at parturition and in the prepartum period, which could indicate a relationship between these immune checkpoints and immunological tolerance during gestation in dairy cattle. In addition, a negative association between the expression of these immune checkpoints prepartum or at parturition and endometrial cytology at T20 and T30 was observed, indicating the negative implications of these immune response regulators in susceptibility to infections. This finding was further corroborated by the relationship between the serum concentration of haptoglobin and the expression of CTLA-4 and PD-1 by T lymphocytes. However, we did not observe a relationship between the indicators of negative energy balance, evaluated by the serum concentrations of BHB and NEFA, and the expression of the immune checkpoint markers studied. Thus, our findings represent an initial step that paves the way for the development of new therapeutic alternatives directed by the host with the objective of increasing the resistance of dairy cattle to infections in this critical period of life.

Keywords: dairy cow; endometrial cytology; endometritis; immune checkpoints; transition period.