This project addresses the functions in vivo of a population of immune effector cells, CD8+ T lymphocytes, in the control of simian immunodeficiency virus (SIV) load and in progression to immunodeficiency disease. We have used treatment with the OKT8F monoclonal antibody (a mouse immunoglobulin IGG) to deplete CD8+ T cells in vivo, with or without thymectomy to achieve long-term depletion. In the preceding year, two animals were treated with antibody and thymectomy. Only a transient (2 weeks) effect was seen. These monkeys were re-treated with antibody 6 months later, to test the hypothesis that their immune response to the mouse immunoglobulin would facilitate T cell depletion by immune clearance mechanisms. However, these two monkeys developed an anaphylactic syndrome during the antibody injection, requiring emergency treatment with dexamethasone and epinephrine. The animals recovered and there was no effect on peripheral blood CD8+ T cells. This concluded the experiment. In the previous year, two thymectomized monkeys were inoculated with pathogenic SIVMAC251 to establish the role of the adult thymus in host immunity to siv. These monkeys survived over two years and were finally euthanized with signs of Simian AIDS at 25 and 26 months post inoculation. This time to disease is at the far end of the normal course of SIV infection in rhesus monkeys. Thus, we conclude that adult thymectomy did not play a significant role in SIV infection and disease progression. For a third experiment two monkeys were treated with OKT8F antibody and inoculated with pathogenic SIV just before the second of three antibody doses. Again, there was a transient disappearance of CD8+ T cells from peripheral blood, lasting 7 to 10 days. There was a sustained elevation in plasma viremia lasting between 6 and 10 weeks, and CTL responses were not detected until 2 months. The monkeys survived over 6 months post inoculation. Thus, initial viral load was elevated but the disease course was not accelerated by transient suppression of CD8+ T cell function during the acute infection.
Showing the most recent 10 out of 408 publications
