Selective Thymocyte Depletion and Immunoglobulin Coating in the Thymus of Cats Infected with Feline Immunodeficiency Virus

Abstract

Thymus alterations associated with feline immunodeficiency virus (FIV), an AIDS animal model, were investigated by measuring phenotypic composition of thymocytes, structure of thymic epithelial cells, and transcription of viral RNA in the thymus of FIV-infected juvenile kittens. These kittens either acquired infection by natural vertical transmission or were experimentally inoculated with the virus at defined times of fetal or neonatal life. Thymocytes from FIV-infected cats were analyzed by flow cytometry for the differential expression of CD4, CD8, Pan T, and IgG and subpopulation percentages were compared to values from uninfected littermates. Infected cats demonstrated a decrease in the percentage of CD4⁺/CD8⁺ lymphocytes and a concurrent increase in the percentage of CD4^-/CD8^-, CD4^-/CD8⁺, and IgG⁺ lymphocytes. Absolute numbers of IgG⁺ cells were increased with FIV infection. On bivariate distribution scatter plots generated by two-color flow cytometry, this population of IgG⁺ cells overlapped extensively with cells having low to minimally detectable levels of a pan-T lymphocyte marker, suggesting that thymocytes were coated with IgG. Immunohistochemical detection of feline IgG defined a broad zone of IgG⁺ cells within the residual cortex but outside lymphoid follicles. However, cells stained with B5, a feline B lymphocyte marker, localized almost exclusively to the centers of lymphoid follicles that were also characterized by a lack of internal cytokeratin staining. FIV RNA transcripts detected by in situ hybridization using an FIV _gag RNA probe were evenly distributed throughout the thymic parenchyma except in lymphoid follicles, which were generally devoid of FIV expression. Despite these phenotypic and structural changes, thymus weight, expressed as a percentage of body weight, was not significantly reduced. From these data, we conclude that the clinically asymptomatic stage of FIV infection is associated with two distinct B cell-related phenomena within the thymus—the formation of germinal centers and the coating of thymocytes with IgG. These changes accompany a distorted thymocyte distribution characterized by a reduced percentage of CD4⁺/CD8⁺ lymphocytes and a relative increase in CD4^-/CD8⁺ and CD4^-/CD8^- lymphocytes. Together, these findings suggest that degenerative thymic changes after lentivirus infection may involve humoral immune mechanisms.