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

Bovine leukemia virus reduces anti‐viral cytokine activities and NK cytotoxicity by inducing TGF‐β secretion from regulatory T cells

“…In further experiments, anti-virus cytokine production was reduced as was shown in our previous reports [23,24,28]. Moreover, CD4 þ CD25 high Foxp3 þ T cell numbers were increased in conjunction with increasing proportions of TGF-b-secreting CD4 þ CD25 high Foxp3 þ T cells, leading to correlations with increased proviral loads in BLV-infected cattle, as shown previously [25,26]. Bovine WC1 þ T cells rather than CD4 þ CD25 þ Foxp3 þ T cells reportedly act as immune regulatory cells [30,34], warranting investigations of WC1 þ T cell kinetics during BLV-infection.…”

“…We recently showed that proportions of Foxp3 þ CD4 þ cells correlate positively with increased lymphocyte numbers, virus titers, and virus loads, and inversely correlate with IFN-g mRNA expression [25]. Moreover, increased TGF-b mRNA expression was correlated with Treg numbers [26], suggesting that bovine Foxp3 þ CD4 þ T cells have immunosuppressive functions during BLV infection. In the present study, we investigated Treg functions by correlating CD4 þ CD25 high Foxp3 þ T cell numbers with T cell responses and NK activity in BLV-infected cattle.…”

“…In previous studies, several factors were shown to play critical roles in the suppression of cellular immune responses and disease progression in BLV-infections [23,24]. Subsequently, we reported that proportions of Foxp3 þ CD4 þ cells were positively correlated with numbers of lymphocytes, virus titers, and virus loads in BLV infected cattle but were inversely correlated with IFN-g expression [25,26]. However, although Foxp3 þ CD4 þ cells downregulate antiviral cytokines, their influence on BLV propagation remains uncharacterized.…”

In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection

“…Another possibility is that the blockade of PD-1/PD-L1 interaction on CD8 + T cells was insufficient to overcome its exhausted status because of other immunoinhibitory molecules like LAG-3, Tim-3 and CTLA-4. Previously, we reported that expression levels of these molecules, LAG-3 [49], Tim-3 [50] and CTLA-4 [51], were upregulated in BLV-infected cattle and that blockades of the interaction between these receptors and their ligands improved immune response in vitro , suggesting their important role during BLV infection. In human and mice, it has been demonstrated that the number of immunoinhibitory receptors concurrently expressed on the same CD8 + T cells affected the severity of T-cell exhaustion during chronic viral infection [52–54].…”

Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses

“…These observations warrant further studies to determine whether PD-1 and LAG-3 are coexpressed to synergistically depress the function of exhausted T cells in Johne's disease. Furthermore, other immunoinhibitory receptors T-cell immunoglobulin domain and mucin domain-3 (Tim-3 [32]) and cytotoxic T-lymphocyte antigen 4 (CTLA-4 [33]) are also likely involved in the development of exhausted T cells in Johne's disease. Accordingly, a recent study showed that CD4 ϩ T cells upregulated CTLA-4 in cattle during the subclinical stage of M. avium subsp.…”