Submitted August 19, 2002
Accepted November 27, 2002
A non-secreted variant of interleukin-4 is associated with apoptosis. Implication for the T helper-2 polarization in HIV-infection
Eric Ledru, Michele Fevrier, Herve Lecoeur, Sylvie Garcia, Severine Boullier, and Marie-Lise Gougeon*
Antiviral Immunity, Biotherapy and Vaccines Unit, Molecular Medicine Department, Institut Pasteur, Paris, France
Viral Immunopathology Laboratory URA CNRS 1930, Molecular Medicine Department, Institut Pasteur, Paris, France
* Corresponding author; email: mlgougeo{at}pasteur.fr.
We report the detection of an IL-4 variant which expression is tightly associated to deprivation apoptosis. It is detected with the 8D4 anti-IL-4 mAb in Th2 but also in Th1 clones, and in primary T cells, and is a non secreted 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 disease, increased expression of IL-4 in T cells is highly correlated to increased apoptosis and is restricted to 8D4 reactivity (r2 = 0.84 between % 8D4-8+ and % 7-AAD+ peripheral T cells, p < 0.0001), and is associated with disease progression. This particular reactivity of patient apoptotic T cells to 8D4 mAb may explain some discordances between studies analysing the Th1/Th2 balance in HIV-infection, and questions the function of this intracellular type 2 signal.
