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Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-08-2499.

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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-4delta 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.

© 2003 by The American Society of Hematology.
 

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