Association of Marek’s Disease induced immunosuppression with activation of a novel regulatory T cells in chickens

Marek’s disease virus (mdv) is an alphaherpesvirus that infects chickens,transforms cd4+t cells and causes deadly lymphomas. in addition,mdv induces immunosuppression early during infection by inducing cell death of the infected lymphocytes,and potentially due to activation of regulatory t (treg)-cells. furthermore,immunosuppression also occurs during the transformation phase of the disease; however,it is still unknown how the disease can suppress immune response prior or after lymphoma formation. here,we demonstrated that chicken tgf-beta+treg cells are found in different lymphoid tissues,with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: ct),fostering an immune-privileged microenvironment exerted by tgf-beta. surprisingly,significantly higher frequencies of tgf-beta+treg cells are found in the spleens of mdv-susceptible chicken lines compared to the resistant line,suggesting an association between tgf-beta+treg cells and host susceptibility to lymphoma formation. experimental infection with a virulent mdv elevated the levels of tgf-beta+treg cells in the lungs as early as 4 days post infection,and during the transformation phase of the disease in the spleens. in contrast to tgf-beta+treg cells,the levels of cd4+cd25+t cells remained unchanged during the infection and transformation phase of the disease. furthermore,our results demonstrate that the induction of tgf-beta+treg cells is associated with pathogenesis of the disease,as the vaccine strain of mdv did not induce tgf-beta+treg cells. similar to human haematopoietic malignant cells,mdv-induced lymphoma cells expressed high levels of tgf-beta but very low levels of tgf-beta receptor i and ii genes. the results confirm that cox-2/ pge2 pathway is involved in immunosuppression induced by mdv-lymphoma cells. taken together,our results revealed a novel tgf-beta+treg subset in chickens that is activated during mdv infection and tumour formation. © 2017 gurung et al.