The applicants propose to utilize the feline immunodeficiency virus (FIV) cat animal model for AIDS to develop a better understanding of the pathogenesis of lentivirus-mediated thymic involution and thymic impairment, and the contribution of thymic lymphopoiesis to immune homeostasis in lentivirus-infected subjects. The pediatric FIV model shows lymph node and thymic lesions similar to those reported in human pediatric AIDS. FIV-infected pediatric and adult cats also have loss of recall antigen responses. Work in their laboratory suggest that in pediatric cats antiviral drug therapy during the acute stage of infection can prevent the loss of T-cells possibly by protecting thymic lymphopoiesis during early life. Further they have evidence from preliminary studies in FIV-infected adults cats, that antiviral therapy stimulates thymic hematopoiesis in a pattern compatible with restoration of thymic T-cell processing. For this proposal, they submit the following specific aims: 1. To measure the contribution of thymic lymphopoiesis to a) the maintenance of peripheral blood T-lymphocyte homeostasis; b) replenishment of T-helper cells depleted by FIV infection and c) regeneration of recall antigen responses lost during FIV infection. 2) To determine if antiviral therapy can: a) prevent thymic involution and loss of thymic lymphopoiesis in FIV-infected pediatric cats; b) allow for reestablishment of thymic lymphopoiesis and restoration of the recall antigen T-cell response in FIV-infected adult cats.
