Characterization of α4β7 integrin and CD32 expression of CD4+ memory T-cell subsets at different stages of HIV infection

Abstract

The human immunodeficiency virus (HIV) causes a chronic infection that, if left untreated, progresses to Acquired Immune Deficiency Syndrome (AIDS). AIDS results from decreasing numbers of CD4+ helper T cells causing a severe immunodeficiency that leaves the body susceptible to a variety of potentially fatal infections and mainly viral-induced cancers, e.g. Kaposi’s Sarcoma. Latently infected CD4+ T cells that persist during infection are highly stable over time and contain replication-competent provirus. Since there is little to no viral gene expression in latently infected CD4+ T cells, it is difficult for the immune system to recognize and eliminate them. It has been suggested that certain T cell subsets, such as central memory T cells, are crucial in the formation of the stable viral reservoir of latently infected T cells. Furthermore, several novel marker molecules to designate latently HIV-infected cells have been proposed. The aim of this thesis was to investigate the expression pattern and potential role of two molecules that could indicate latently infected cells (CD32a) or be involved in the formation of the reservoir (α4β7) in CD4+ T cell memory subsets in a large cohort of HIV-infected individuals with different clinical disease course (HIV patients with detectable viremia, antiretroviral therapy- (ART-) suppressed patients with undetectable viral load and elite controllers controlling the infection without medication). In addition to peripheral blood mononuclear cells (PBMC), lymph node mononuclear cells (LNMC) as well as gut lamina propria lymphocytes (LPL) were studied with regard to the surface expression of CD32 and α4β7. T-cell subsets of PBMC and LPL from patients with ulcerative colitis (UC) were studied to investigate the homing capacity of a certain T-cell subset to the gut as well as the eligibility of a therapeutic α4β7-specific antibody to potentially inhibit the HIV reservoir formation within the gut.