Blood, 15 April 2003, Vol. 101, No. 8, pp. 3102-3105
BRIEF REPORT: IMMUNOBIOLOGY
A nonsecreted variant of interleukin-4 is associated with
apoptosis: implication for the T helper-2 polarization in HIV
infection
Eric Ledru,
Michèle Février,
Hervé Lecoeur,
Sylvie Garcia,
Séverine Boullier, and
Marie-Lise Gougeon
From the Antiviral Immunity, Biotherapy, and Vaccines
Unit and the Viral Immunopathology Laboratory Unité de Recherche
Associée Centre National de la Scientifique (URA CNRS) 1930, Molecular Medicine Department, Institut Pasteur, Paris,
France.
We report the detection of an interleukin-4 (IL-4) variant
whose expression is tightly associated with deprivation apoptosis. It
is detected with the 8D4 anti-IL-4 monoclonal antibody (mAb) not only in T helper-2 (Th2) but also in Th1 clones, and
primary T cells, and it is a nonsecreted molecule. It is not expressed during primary necrosis. Our data suggest that de novo IL-4
transcription of an alternative IL-4 mRNA
(IL-4
13) is induced during deprivation apoptosis. In HIV-infected patients, increased expression of IL-4 in T
cells is highly correlated to increased apoptosis, restricted to 8D4
reactivity (r2 = 0.84 between % 8D4-8+ and % 7- amino-actinomycin D-positive
[7-AAD+] peripheral T cells, P < .0001),
and associated with disease progression. The particular reactivity of
apoptotic T cells to 8D4 mAb may explain some discordances among
studies analyzing the Th1/Th2 balance in HIV infection and questions
the function of this intracellular type 2 signal.