AN IMMUNOHISTOLOGIC STUDY OF GRANULOMATOUS INFLAMMATION IN SIV-INFECTED RHESUS-MONKEYS

We studied granulomatous inflammation in simian AIDS using histologic, immunohistologic, and in situ hybridization techniques. Complete Freund's adjuvant was used to induce granulomas in two control animals and two macaques infected with simian immunodeficiency virus (SIV) and having low peripheral CD4+ T cell counts. Control animals developed large ( > 2 cm diameter) epithelioid granulomas containing CD68+ macrophages (mphis), epithelioid mphis and multinucleated giant cells (MNGCs), CD4+ and CD8+ T cells, and small perivascular collections of CD20+ B cells. Lymphocytes rarely expressed proliferating cell nuclear antigen (Ki-67), and only rare endothelial cells expressed vascular cell adhesion molecule 1 (VCAM-1). In contrast, SIV+ animals had smaller (<0.5 cm diameter) epithelioid granulomas characterized by numerous large, dense CD8+, CD20+ lymphocyte aggregates with prominent local division (Ki-67+). Despite low blood CD4+ T cell numbers, there was a substantial CD4+ T cell infiltrate, accompanied by enhanced endothelial VCAM-1 expression. These granulomas contained no detectable SIV antigen or RNA. Thus, in simian AIDS, experimentally induced granulomatous responses are grossly attenuated, yet associated with increased local endothelial-leukocyte signaling and lymphocyte division.