CD8 + Thymic Lymphocytes Express Reduced Levels of CD8β and Increased Interferon γ in Cats Perinatally Infected with the JSY3 Molecular Clone of Feline Immunodeficiency Virus

Abstract

Biological isolates of feline immunodeficiency virus (FIV) cause a relative expansion of activated single-positive CD8⁺ (SP CD8⁺) lymphocytes within the thymus of infected cats. In this study, thymic SP CD8⁺ lymphocytes were analyzed from cats inoculated as neonates with a pathogenic molecular clone of FIV, JSY3, which was previously derived from the wild-type biological isolate FIV_NCSU-1 (NCSU-1). Four cats were inoculated intraperitoneally with NCSU-1 and compared with 11 cats inoculated with JSY3. Five control cats matched in litter and age were administered an intraperitoneal sham inoculum. Between 12 and 16 weeks postinoculation, interferon-γ (IFN-γ) mRNA was quantified by RT-PCR in freshly isolated thymocytes and peripheral blood mononuclear cells (PBMCs). The quantity of IFN-γ mRNA was increased more than 10-fold in thymocytes and PBMCs of 13 of 13 FIV-inoculated cats as compared with the sham-inoculated controls. IFN-γ mRNA coenriched with magnetically sorted CD8⁺ PBMCs and single-positive (SP) CD8⁺ thymocytes. Cells expressing IFN-γ mRNA were located within the thymic perivascular zone, along the corticomedullary junction, and adjacent to lymphoid follicles. The expansion of thymic SP CD8⁺ cells was associated with an increase in CD8α⁺/β^neg and CD8α⁺/β^lo phenotypes, the latter population resembling a previously reported memory/effector peripheral blood cell with FIV suppressor activity. From these data we conclude that JSY3 and NCSU-1 induce similar phenotypic changes in thymic and peripheral blood CD8⁺ cells. Thus, JSY3 is pathogenic for the thymus in vivo and will be useful for defining determinants of the CD8⁺ cell response in this pediatric AIDS model.