Differential Thrombospondin Expression on T Lymphocytes in a Feline Immunodeficiency Virus Model

Abstract

CD4+CD25+ T regulatory cells represent an important subset of lymphocytes whose function is to suppress autoimmune disease and control normal immune responses. There is much research indicating a direct role for TGF-beta expressed on the surface of Tregs in the suppressor function of these cells. TGF-beta, whether bound to the cell surface or secreted, is produced as part of a complex that renders the cytokine inactive. Thrombospondin is the primary activator of biologically latent TGF-beta. This research demonstrates that thrombospondin is expressed on the surface of T lymphocytes isolated from the blood and lymph nodes of normal and FIV positive felines. Thrombospondin is expressed at significantly higher levels on CD4+CD25+ T lymphocytes, but can be induced in culture by activating T helper cells in the presence of LPS and IL2. We also observed that the CD4+CD25- T helper cells isolated from FIV negative control lymph nodes were able to markedly upregulate surface thrombospondin expression compared with similarly stimulated CD4+CD25- T helper cells from FIV positive sources. These findings are initial steps in working to understand the mechanism behind latent TGF-beta activation on CD4+CD25+ T regulatory cells and the role this cell type plays in FIV/HIV pathogenesis.