Open AccessAssociation of Marek’s Disease induced immunosuppression with activation of a novel regulatory T cells in chickens
Author(s) -
Angila Gurung,
Nitin Machindra Kamble,
Benedikt B. Kaufer,
Ansar A. Pathan,
Shahriar Behboudi
Publication year - 2017
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006745
Subject(s) - immune system , immunosuppression , biology , immunology , il 2 receptor , lymphoma , haematopoiesis , pathogenesis , virology , cancer research , t cell , stem cell , microbiology and biotechnology
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.