Short-termed expression of interleukin-12 during experimental BLV infection may direct disease progression to persistent lymphocytosis

Yakobson, Bracha; Brenner, J.; Ungar-Waron, Hanna; Trainin, Z.

doi:10.1016/s0165-2427(98)00136-6

Cited by 29 publications

(21 citation statements)

References 21 publications

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“…Later, they have also reported that cattle in SP expressed much more amount of IL-12, which is a key cytokine that induce Th1 responses, though those were downregulated in cattle with progressed disease stages [50]. This finding was supported by the report by Yakobson et al, showing that IL-12 expressions were increased at the early phase of infection, while those of IL-10 were induced in the PBMC of cattle, in which BLV replicated [69]. Thus, Th1 cytokines, which play important role to induce CMI was supposed to be critical to prevent disease progression of the BLV infection.…”

Section: Change Of Cytokine Profiles Associated With Disease Progressmentioning

confidence: 77%

Host Immune Responses in the Course of Bovine Leukemia Virus Infection.

Kabeya

Ohashi

Onuma

2001

The Journal of Veterinary Medical Science

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ABSTRACT. Bovine leukemia virus (BLV) is a type C retrovirus infecting bovine B cells and causing enzootic bovine leukosis. Since it takes long periods to develop the disease, it is believed that BLV and host immune responses are closely related. In this review, the accumulated data showing close relationship between BLV and host immune responses are summarized in 4 sections. First, we discuss the role of cell-mediated immunity in protecting hosts from BLV infection. Second, several reports showing the relationship between the disease progression and the change of cytokine profiles are summarized. In the third section, we have focused on tumor necrosis factor α (TNFα) and its two types of receptors, and the possible involvement of TNF α in the BLV-induced leukemogenesis is discussed. The expression of TNF α has been shown to be regulated by major histocompatibility complex (MHC) haplotype. The resistance to BLV infection is supposed to be established by some innate factors, which are closely related to MHC haplotype. Finally, we propose that a breeding strategy based on the MHC haplotype could be a good approach to control BLV infection. This review includes some recent data from us and other groups. KEY WORDS: bovine leukemia virus, cell-mediated immunity, cytokine profile, major histocompatibility complex, tumor necrosis factor α.J. Vet. Med. Sci. 63 (7): [703][704][705][706][707][708] 2001 Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis, is an oncogenic B-lymphotropic retrovirus [27]. The disease is divided into three stages; serologically positive, but negative for lymphocytosis (SP); serologically positive and positive for persistent lymphocytosis (PL); and leukemia. Like other members of chronic retrovirus infection, BLV infection results in a prolonged asymptomatic period with a low viral load that persists for 1 to 8 years. Thirty percent of infected animals progress to PL, characterized by a polyclonal expansion of B cells. Only 0.1 to 10 percent develop malignant lymphosarcoma [53]. Usually a long duration is required between these disease stages suggesting that BLV modulate host immune systems [22,23].The purpose of this review is to assemble the results of studies on the host immune responses in the course of BLV infection in an effort to provide a picture towards the control of BLV infection. CELL-MEDIATED IMMUNITY AND BLV INFECTIONBoth humoral and cell-mediated immunity (CMI) are known to be induced in natural BLV-infection, and these play roles in protection of hosts from BLV infection [20,29,41,42,45]. However, their relative roles in protection remain to be elucidated. In this regard, a series of recent studies have postulated that particularly CMI against BLV antigens contributes to the suppression of BLV replication, this leading to the delay of disease progression [42,59]. Orlik and Splitter have shown that CMI responses to BLV antigens were suppressed in correlation to disease progression [46]. The positive effect of indomethacin on the recovery of the suppres...

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Section: Change Of Cytokine Profiles Associated With Disease Progressmentioning

confidence: 77%

Host Immune Responses in the Course of Bovine Leukemia Virus Infection.

Kabeya

Ohashi

Onuma

2001

The Journal of Veterinary Medical Science

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“…In particular, the Th1 cytokine productions such as IFN-γ are closely associated with disease resistance in viral infections. In BLV infection, the relationship between resistance or sensitivity to development of PL and several cytokines have been reported, such as IL-2, IL-10, IL-12 and IFN-γ (20,21,37,38,46,47). Most of these reports have suggested that it is important to induce cellular immunity by Th1 cytokine for protection against the development of disease as well as other infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Ovine MHC Class IIDRB1Alleles on Immune Response in Bovine Leukemia Virus Infection

Konnai

Takeshima

Tajima

et al. 2003

Microbiology and Immunology

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We have reported previously that the alleles of the ovine leukocyte antigen (OLA)‐DRB1 gene that encode the Arg‐Lys (RK) motif and the Ser‐Arg (SR) motif at positions β70/71 of the OLA‐DRβ1 domain are associated with resistance and susceptibility, respectively, to development of bovine leukemia virus (BLV)‐induced ovine lymphoma. Here, to investigate the different immune response in sheep that carried alleles associated with resistance and susceptible for 30 weeks after infection with BLV, we selected sheep that had the RK/RK or SR/SR genotype among the 52 sheep analyzed by polymerase chain reaction‐restriction fragment length polymorphism and DNA sequencing of PCR product for the OLA‐DRB1 exon 2 and infected them with BLV. Although the number of BLV‐infected cells and virus titer had been maintaining low levels throughout the experimental period, the sheep with the RK/RK genotype could induce expansion of CD5− B‐cells and rapid production of neutralizing antibody in the early phase of infection. The level of incorporation of [3H]thymidine by peripheral blood mononuclear cells from the sheep with RK/RK genotype gave a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T‐helper epitope of the BLV envelope glycoprotein gp51. In contrast, the sheep with SR/SR genotype showed a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T‐cytotoxic and B‐cell epitopes. In such cases, the animals with the RK/RK strongly expressed IFN‐7, the animals with SR/SR genotype strongly expressed IL‐2. To determine the proliferating cells, we tried a blocking assay with monoclonal antibodies such as anti‐CD4, ‐CD8 and ‐DR molecule. We found that these proliferating cells were MHC‐restricted CD4+ T‐cells.

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“…Similar results were also observed in macrophages of PL cattle (Pyeon et al 1996). Additionally, Yakobson et al (1998Yakobson et al ( , 2000 confirmed that, in contrast to other cytokines, an elevated level of IL-10 is a distinctive feature of the late stage of BLV infection; furthermore, a systematic increase in its concentration can indicate disease progression. Elevated concentration of IL-10 and its dependence on infection stage was also confirmed in the serum of experimentally infected sheep (Szczotka 2007).…”

Section: Discussionmentioning

confidence: 68%

“…It is one of the most important cytokines in the polarisation of naive T cells to interferon producing Th1 (Lucey et al 1996, Yakobson et al 1998, Pyeon and Splitter 1999. It has been shown that IL-12 can stimulate the expression of Th1 cytokines, actively counteracts apoptotic processes and that it has strong antitumoral and antiviral properties.…”

Section: Discussionmentioning

confidence: 99%

Cytokine profiles of dendritic cells (DCs) during infection with bovine leukaemia virus (BLV)

Iwan

Szczotka

Kocki

2017

Polish Journal of Veterinary Sciences

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BLV is an agent of enzootic bovine leukaemia (EBL), an infectious disease affecting cattle worldwide. BLV infection has been associated with immune system disorders and discrepancies in the cytokine network. The significance of dendritic cells in the pathogenesis of BLV infection is largely unknown, but considering their fundamental role in immune response it may be crucial. DCs precursors were isolated with the use of immunomagnetic beads from BLV-infected and BLV-free cows. From these precursors cultures of monocyte derived dendritic cells (MoDCs) were generated with the use of a cytokine cocktail (IL-4 and GM-CSF). Additionally, parallel DCs from BLV-negative animals were infected in vitro. The level of cytokines: IL-6, IL-10, IL-12(p40), IL-12(p70) was determined in DC cultures: infected in vitro, originating from naturally infected cattle and BLV-free cattle. The investigation showed significant changes in almost all analyzed populations of BLV-infected DCs. Cytokine profiles of blood MoDCs indicated activation of these groups during infection. In the case of spleen MoDCs and lymph node MoDCs a decrease in production of IL-12(p40) and IL-12(p70) in favour of IL-6 and IL-10 was noted, suggesting promotion of BLV infection development.

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Short-termed expression of interleukin-12 during experimental BLV infection may direct disease progression to persistent lymphocytosis

Cited by 29 publications

References 21 publications

Host Immune Responses in the Course of Bovine Leukemia Virus Infection.

Host Immune Responses in the Course of Bovine Leukemia Virus Infection.

The Influence of Ovine MHC Class IIDRB1Alleles on Immune Response in Bovine Leukemia Virus Infection

Cytokine profiles of dendritic cells (DCs) during infection with bovine leukaemia virus (BLV)

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