Blockade of BTLA alone or in combination with PD-1 restores the activation and proliferation of CD8+ T cells during in vitro infection with NCP BVDV.
Vet Microbiol
; 290: 110004, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38281324
ABSTRACT
Bovine viral diarrhea virus (BVDV) infection can result in typical peripheral blood lymphopenia and immune dysfunction. However, the molecular mechanism underlying the onset of lymphopenia remains unclear. B and T lymphocyte attenuator (BTLA) is a novel immune checkpoint molecule that primarily inhibits activation and proliferation of T cells. Blockade of BTLA with antibodies can boost the proliferation and anti-viral immune functions of T cells. Nonetheless, the immunomodulatory effects of BTLA in CD8+ T cells during BVDV infection remain unknown. Therefore, BTLA expression was measured in bovine peripheral blood CD8+ T cells infected with BVDV in vitro. Furthermore, the effects of BTLA or PD-1 blockade on CD8+ T cell activation, proliferation, and anti-viral immunological activities were investigated, as well as expression of signaling molecules downstream of BTLA, both alone and in combination. The results demonstrated that BTLA and PD-1 mRNA and protein levels were considerably increased in CD8+ T cells infected with cytopathic and non-cytopathic (NCP) BVDV. Surprisingly, as compared to blockade of either BTLA or PD-1, blockade of both dramatically increased proliferation and expression of CD25 and p-EKR of CD8+ T cells infected with NCP BVDV. Furthermore, blockade of BTLA, but not PD-1, had no effect on BVDV replication or IFN-γ expression. These findings confirmed the immunomodulatory roles of BTLA during BVDV infection, as well as the synergistic role of BTLA and PD-1 in NCP BVDV infection, thereby providing new insights to promote activation and the anti-viral immunological activities of CD8+ T cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Diarreia Viral Bovina
/
Vírus da Diarreia Viral Bovina Tipo 1
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Linfopenia
Limite:
Animals
Idioma:
En
Revista:
Vet Microbiol
Ano de publicação:
2024
Tipo de documento:
Article