Increased expression of the regulatory T cell-associated marker CTLA-4 in bovine leukemia virus infection.

Abstract

Regulatory T cells (Tregs) play a critical role in the maintenance of the host's immune system. Tregs, particularly CD4(+)CD25(+)Foxp3(+) T cells, have been reported to be involved in the immune evasion mechanism of tumors and several pathogens that cause chronic infections. Recent studies showed that a Treg-associated marker, cytotoxic T-lymphocyte antigen 4 (CTLA-4), is closely associated with the progression of several diseases. We recently reported that the proportion of Foxp3(+)CD4(+) cells was positively correlated with the number of lymphocytes, virus titer, and virus load but inversely correlated with IFN-γ expression in cattle infected with bovine leukemia virus (BLV), which causes chronic infection and lymphoma in its host. Here the kinetics of CTLA-4(+) cells were analyzed in BLV-infected cattle. CTLA-4 mRNA was predominantly expressed in CD4(+) T cells in BLV-infected cattle, and the expression was positively correlated with Foxp3 mRNA expression. To test for differences in the protein expression level of CTLA-4, we measured the proportion of CTLA-4-expressing cells by flow cytometry. In cattle with persistent lymphocytosis (PL), mean fluorescence intensities (MFIs) of CTLA-4 on CD4(+) and CD25(+) T cells were significantly increased compared with that in control and aleukemic (AL) cattle. The percentage of CTLA-4(+) cells in the CD4(+) T cell subpopulation was positively correlated with TGF-β mRNA expression, suggesting that CD4(+)CTLA-4(+) T cells have a potentially immunosuppressive function in BLV infection. In the limited number of cattle that were tested, the anti-CTLA-4 antibody enhanced the expression of CD69, IL-2, and IFN-γ mRNA in anti-programmed death ligand 1 (PD-L1) antibody-treated peripheral blood mononuclear cells from BLV-infected cattle. Together with previous findings, the present results indicate that Tregs may be involved in the inhibition of T cell function during BLV infection.

• Authors: Saori Suzuki, Satoru Konnai, Tomohiro Okagawa, Ryoyo Ikebuchi, Asami Nishimori, Junko Kohara, Claro N Mingala, Shiro Murata, Kazuhiko Ohashi
• Journal: Veterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 163 Issue 3-4 Pg. 115-24 (Feb 15 2015) ISSN: 1873-2534 [Electronic] Netherlands
• PMID: 25618590 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• CTLA-4 Antigen
• Cytokines
• DNA-Binding Proteins
• Forkhead Transcription Factors
• RNA, Messenger

Topics

• Amino Acid Sequence
• Animals
• CTLA-4 Antigen (genetics, metabolism)
• Cattle
• Cloning, Molecular
• Cytokines (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Enzootic Bovine Leukosis (metabolism)
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Expression Regulation, Viral (immunology)
• Leukemia Virus, Bovine (immunology)
• Molecular Sequence Data
• Phylogeny
• RNA, Messenger (genetics, metabolism)
• T-Lymphocytes, Regulatory (metabolism)