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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2695-2701
IMMUNOBIOLOGY
HIV-specific effector cytotoxic T lymphocytes and HIV-producing
cells colocalize in white pulps and germinal centers from
infected patients
Anne Hosmalin,
Assia Samri,
Marie-Jeanne Dumaurier,
Yasmine Dudoit,
Eric Oksenhendler,
Marina Karmochkine,
Brigitte Autran,
Simon Wain-Hobson, and
Rémi Cheynier
From Unité INSERM 445, Institut Cochin de
Génétique Moléculaire; Laboratoire d'Immunologie
Cellulaire et Tissulaire, Hôpital de la
Pitié-Salpêtrière; Unité de
Rétrovirologie Moléculaire, Institut Pasteur; Service
d'Immuno-Hématologie, Hôpital St Louis; and Service
d'Immunologie Clinique, Hôpital Européen Georges Pompidou;
all of Paris, France.
Human immunodeficiency virus (HIV) infection is characterized by
the massive infiltration of secondary lymphoid organs with activated
CD8+ T lymphocytes. While converging data indicated that
these cells were HIV-specific cytotoxic 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 pulps from an untreated patient and in 1 of 24 tonsil germinal centers from a second
patient with incomplete viral suppression following bitherapy. These
patients had plasma HIV RNA loads of 5900 and 820 copies per
milliliter. The 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 structures tested.
Conversely, CTL activity was not found in spleens from 2 patients under
highly active antiretroviral therapy, with undetectable plasma viral
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 viral replication in immunocompetent
structures of secondary lymphoid organs triggers anti-HIV effector CTLs
to these particular locations, providing clues to target therapeutic intervention.
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