Alterations in T-cell subsets in SIV-infected rhesus monkeys
Project management at the University of Würzburg:
HIV-infection leads to reduced numbers of CD4+ T-cells in blood and concomitantly induces AIDS. However, the exact pathogenetic mechanisms are not completely understood. This is partly due to a lack of information about the earliest phases of the infection and about the situation in the lymphatic organs, which harbor more than 80% of the total lymphocyte pool. Therefore, we have investigated alterations in the composition of lymphocytes during the first months of infection in the animal model of infection of rhesus monkeys with simian immunodeficiency viruses (SIV). The findings were correlated with the course of the disease. We demonstrated differences in the kinetics of CD4+ and CD8+ T-cell subsets already during the first two weeks of infection. During primary viraemia, about half of cytotoxic T-cells are proliferating. These cells remain activated during the course of the infection. In contrast, the proliferation rate of CD4+ T-helper cells is initially reduced but is later increased above preinfection levels in slow progressors. In parallel, infection leads to a selective loss of CD29+ memory T-helper cells. This parameter can be used as a prognostic marker for disease progression already at 4 weeks post infection. The reduction of CD4+ T-cells is less pronounced in lymph nodes. In this compartment, the number of lymphocytes even increases suggesting that the loss in blood probably depends in part on an altered distribution. In addition, we could demonstrate that certain MHC-alleles are associated with rapid disease progression. Based on these immunogenetic markers it is possible to preselect monkeys with a certain susceptibility already before infection.
Projekt period: from 01.1999 to 12.2001