FIV Infection Induces Unique Changes in Phenotype and Cellularity in the Medial Iliac Lymph Node and Intestinal IEL

Studies of human immunodeficiency virus-1 (HIV-1)-infected patients and simian immunodeficiency virus (SIV)-infected macaques have identified profound depletion of CD4⁺ T cells and expansion of CD8⁺ T cells in the gastrointestinal lamina propria. Less attention has been given to CD8⁺ intraepithelial lymphocytes (IEL), and no studies have concurrently examined inductive sites such as draining lymph nodes. Our preliminary data in the feline immunodeficiency virus (FIV) animal model suggested additional changes in IEL, and marked differences in the responses of lymph nodes draining different mucosal sites. To address this, we quantified the absolute leukocyte yield and examined the phenotype of cells from small intestinal IEL, mesenteric lymph node (MLN), and medial iliac lymph node (ILN) from chronically FIV-infected cats. The cellularity of the ILN was increased 530% in FIV-infected animals with an expansion of CD62L⁺ cells, suggesting an increased population of naive T cells. The number of CD4⁺, as well as CD8⁺, T cells was increased in the ILN, resulting in a CD4:CD8 ratio greater than 1:1. In contrast, reduced cellularity, specific loss of CD4⁺ T cells, and inversion of the CD4:CD8 ratio was observed in the MLN, which drains the intestine. In IEL, loss of CD8α, CD8β, and CD4-expressing T cells was found in FIV-infected cats. Furthermore, expression intensity of CD8α and CD5, markers known to be important in T cell function, was markedly decreased on IEL. These findings expand the array of immune alterations induced by lentiviral infection and indicate that characterization of multiple mucosal sites will be necessary to fully understand the pathogenesis of HIV-1 infection.