Marek’s disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response

Abstract

The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek’s disease (MD) which is caused by an oncogenic herpesvirus; Marek’s disease virus (MDV). To determine differential functional abilities of T cells associated with resistance and susceptibility to MD, we identified immunodominant CD4+TCRvβ1 T cell epitopes within the pp38 antigen of MDV in B19 and B21 MHC haplotype chickens using an ex vivo ELISPOT assay for chicken IFN-gamma. These novel pp38 peptides were used to characterize differential functional abilities of T cells as associated with resistance and susceptibility to MD. The results demonstrated an upregulation of cytokines (IL-2, IL-4, IL-10) and lymphocyte lysis-related genes (perforin and granzyme B) in an antigen specific manner using RT-PCR. In the MD-resistant chickens (B21 MHC haplotype), antigen-specific and non-specific response was highly skewed towards Th2 response as defined by higher levels of IL-4 expression as well as lymphocyte lysis-related genes compared to that in the MD-susceptible chicken line (B19 MHC haplotype). Using CD107a degranulation assay, the results showed that MDV infection impairs cytotoxic function of T cells regardless of their genetic background. Taken together, the data demonstrate an association between type of T cell response to pp38 and resistance to the disease and will shed light on our understanding of immune response to this oncogenic herpesvirus and failure to induce sterile immunity.

Activated Chicken Gamma Delta T Cells Are Involved in Protective Immunity against Marek’s Disease

“…It has been reported that IFN-γ produced by activated human γδ T cells initiates a T helper type 1 (Th1) response via the induction of Th1-promoting dendritic cells (DCs) [ 30 , 31 , 32 ]. We also demonstrated an association of the induction of a potent anti-MDV Th1 response with resistance to MD [ 33 , 34 ]. Our results showing that Th1 cytokines, IFN-γ and IL-2, were upregulated and one of the anti-inflammatory cytokines, TGF-β, was downregulated in ex vivo-stimulated PBMCs with anti-TCRγδ mAb and in the spleen after the infusion of ex vivo-stimulated PBMCs at the transcript level indicate that activated chicken γδ T cells may contribute to the initiation of the Th1 response, which is shown to be important for the control of MD-lymphoma ( Figure 2 ).…”

Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use

“…In chickens, the two T-cell lineages can be distinguished based on the types of chains they possess, which include αVβ1 and αVβ2 chains. T cells expressing αVβ1 chains from infected or vaccinated chickens, but not naïve birds, recognize peptides from avian viruses in association with classical MHC molecules ( 46 ). Thus, T cells expressing αVβ1 chains are part of adaptive immunity.…”

“…Thus, T cells expressing αVβ1 chains are part of adaptive immunity. However, it remains unclear whether T cells expressing αVβ2 chains are also part of adaptive immunity, as no specific antigens recognized by this TCR have yet been identified ( 46 ). Moreover, the CD4 and CD8 co-receptors, which bind to major histocompatibility (MHC) I and MHC II, respectively, have also been identified in chickens and allow for further classification.…”

“…Moreover, the CD4 and CD8 co-receptors, which bind to major histocompatibility (MHC) I and MHC II, respectively, have also been identified in chickens and allow for further classification. However, unlike in mammals, a clear distinction of cell populations into cytotoxic and helper cells has not been demonstrated, but evidence suggests that both conventional CD4 + and CD8 + cells and innate-like T cells, such as γδ T cells, are involved in the control of pathogens via cytotoxicity or production of cytokines ( 46 – 52 ).…”

Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro

“…MDV replicates and sheds from feather follicle epithelial cells and intermediate epidermal layers of the foot skin in cell-free form into the environment [ 1 , 9 ]. Vaccination induces anti-MDV T cell responses [ 10 , 11 ], which reduce host symptoms and prolong survival, but it fails to inhibit virus replication and shedding [ 1 ]. Failure to induce sterile immunity has led to the emergence of more virulent MDV [ 12 ].…”