HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients

Human immunodeficiency virus (HIV) infection is characterized by the massiv e infiltration of secondary lymphoid organs with activated CD8(+) T lymphoc ytes. While converging data indicated that these cells were HIV-specific cy totoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lacking. Here, the presence of HIV-specific effector CTLs was demonstrated directly ex vivo in 15 of 24 microdissected splenic white pulp s from an untreated patient and in 1 of 24 tonsil germinal centers from a s econd patient with incomplete viral suppression following bitherapy. These patients had plasma HIV RNA loads of 5900 and 820 copies per milliliter. Th e frequencies of HIV-1 DNA(+) cells in their lymphoid organs were more than 1 in 50 and 1 in 175, respectively. Spliced viral messenger RNA (a marker for ongoing viral replication) was present in most immunocompetent structur es tested. Conversely, CTL activity was not found in spleens from 2 patient s under highly active antiretroviral therapy, with undetectable plasma vira l load. These patients had much lower spleen DNA(+) cell frequencies (1 in 2700 and 1 in 3800) and no white pulps containing spliced RNA. CTL effector activity as well as spliced viral messenger RNA were both concentrated in the white pulps and germinal centers. This colocalization indicates that vi ral replication in immunocompetent structures of secondary lymphoid organs triggers anti-HIV effector CTLs to these particular locations, providing cl ues to target therapeutic intervention. (Blood. 2001;97:2695-2701) (C) 2001 by The American Society of Hematology.