The Role of CD8 on CD4+ T Cells

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): There are many mechanisms that contribute to the decline of the immune response in HIV disease. Infection and perturbation of CD4+ T cells by HIV dramatically contributes to viral replication and a decreased ability to respond to antigenic insult. There are many different functional subsets of CD4+ T cells, and HIV appears to target the highly activated populations, particularly those cell that specifically respond to HIV infected cells. We have shown that CD4 expression by CD8+ T cells plays an important role in CD8 cell function. Recently, our laboratory has identified a highly activated population of CD4+ T cells that express the CD8 molecule. Preliminary studies indicate that this population is more abundant in HIV-infected people and may reflect the greater levels of cellular activation seen in these individuals. This high level of activation could render these cells more susceptible to infection and destruction by HIV. This proposal describes studies that examine the function of this subset and the role of the CD8 molecule on CD4+ T cells. We will examine the expression of this molecule during CD4+ T cell activation, as well as the phenotypic and function characteristics of this cell type. We will investigate the following three Specific Aims: 1) Further explore the acquisition of CD8 expression by CD4+ T cells, 2) Determine the function of the CD8 molecule on CD4+ T cells, 3) To examine the functional role of CD8 expression on CD4+ T cells in vivo in response to viral infection and alloantigen. The experiments outlined in this proposal will help us understand the role of CD8 on CD4+ T cells and the effects of HIV infection on this subset. Further, it will allow us to determine the function of the CD4+CD8dim subset seen in vivo. These studies combined will allow us to determine the possible effects that the appearance or loss of this subset may have on HIV disease progression and antiviral immunity.