Kinetik von NK-Zellen und gamma-delta-T-Zellen nach Infektion von Rhesusaffen mit Immundefizienzviren

Abstract

Human immunodeficiency virus (HIV) infection and the caused acquired immunodeficiency syndrome (AIDS) developed over the last 25 years to a pandemic. In 2006 more than 39 Million people were HIV positive. Based on the high concordance with the human and viral system, rhesus macaques infected with simian immunodeficiency virus (SIV) currently provide one of the best animal models to study pathogenesis. In this study, to analyze disease progression kinetics of different lymphocyte populations were determined. We focussed on NK cells and gamma-delta-TCR positive T cells as both belong to the cellular immune response early post HIV/SIV-infection. In addition both populations can activate the adaptive immune response by cytokine secretion. To obtain NK cells and gamma-delta-TCR positive T cells, peripheral blood mononuclear cells (PBMC) were isolated and stained with fluorescence labelled mononuclear antibodies. Samples were measured on a multicolour flow cytometer and subsequently twelve parameter analyses, including size and inner complexity characteristics, were performed. Changes in the frequency of NK cells and their differentiation were detected, after definition as lineage marker negative CD16 and/or CD159a expressing cells. Early post infection the proportion of NK cells was increased, normalized to the pre infection data, and peaked at the beginning of the post acute phase. At following time points there was a decrease to pre infection levels. The examined subpopulations showed distinct changes in the CD159a expression, an antigen that is part of a receptor inhibiting NK cell cytotoxicity. Also very soon post infection the proportion of gamma-delta-TCR positive cells significantly increased in relation to the T cell population in general. After reaching the maximum at the beginning of the post acute phase the frequency of gamma-delta-TCR positive T cells remains increased. The two subpopulations of CD69 and CD159a expressing gamma-delta-TCR positive T cells subpopulations over-average increase, that last to the chronic phase. The observed changes of these two populations in proportion and function clearly demonstrate their role as part of the innate immune system in recruiting the specific immune response early post SIV infection.