A nonsecreted variant of interleukin-4 is associated with apoptosis: implication for the T helper-2 polarization in HIV infection.
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 delta(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 (r(2) = 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.
Ledru
Eric
E
Antiviral Immunity, Biotherapy, and Vaccines Unit and the Viral Immunopathology Laboratory Unité de Recherche Associée Centre National de la Scientifique 1930, Molecular Medicine Department, Institut Pasteur, Paris, France.
Février
Michèle
M
Lecoeur
Hervé
H
Garcia
Sylvie
S
Boullier
Séverine
S
Gougeon
Marie-Lise
ML
D017398:Alternative Splicing; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017209:Apoptosis; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018613:Microscopy, Confocal; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D020033:Protein Isoforms; D003609:Dactinomycin; D015847:Interleukin-4; C025942:7-aminoactinomycin D