Feline Lentivirus enhanced CD4+CD25+ T regulatory conversion of CD4+CD25- T cells to phenotypic and functional T reg cells via the TGF-b/TGF-bR signaling pathway
The human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) pandemic continues to escalate with over 40 million people now living with HIV/AIDS and 5 million new infections reported in 2003. Development of an effective vaccine is crucial for the prevention and possible eventual eradication of the disease. However, vaccines do not alleviate the need for new treatment strategies for individuals already infected and living with HIV/AIDS. Currently, the most effective treatment employs highly active anti-retroviral therapy (HAART) which is effective in decreasing plasma virus load, but infected cells producing virus remain. Modulation of the host immune response may prove to be an effective and long-term solution to control established HIV infection. To use this strategy, a more thorough understanding of the pathology of HIV infected cells is needed. Cell types permissive to HIV and feline immunodeficiency virus (FIV) infection include CD4 and CD8 T cells, macrophages, and dendritic cells. Interestingly, a subset of CD4 T cells, CD4+CD25+ T regulatory cells, is productively infected with both HIV in humans and feline immunodeficiency virus (FIV) in cats and may serve as a long-term virus reservoir.
In this study, we investigated the possibility of peripheral generation of Treg-like cells from CD4+CD25- T cells in a TGF-b/TGF-bRII signaling dependent manner mediated by CD4+CD25+ T regulatory cells. While CD4+CD25- T cells from both control and FIV-infected animals are subject to CD4+CD25+ T regulatory cell mediated conversion to a Treg-like phenotype, freshly isolated Treg cells from FIV-infected and not control cats exerted this conversion. Further understanding of the mechanisms involved in the homeostasis of CD4+CD25+ T regulatory cells in the periphery may provide a strategy to control expansion of HIV/FIV virus reservoirs and immune suppression and, therefore, control disease progression.
Advisor:Dr. Frederick Fuller; Dr. Linda Martin; Dr. Gregg Dean; Dr. Wayne Tompkins
School:North Carolina State University
School Location:USA - North Carolina
Source Type:Master's Thesis
Date of Publication:08/10/2006