HIV-induced IL-6/IL-10 dysregulation of CD4 cells is associated with defective B cell help and autoantibody formation against CD4 cells

To analyse CD4 cell cytokine secretion and helper/suppressor function at a clonal level we established 446 CD4+ T cell clones (TCC) in four healthy controls, three HIV− haemophilia patients, four CDC II,III and four CDC IV patients. Spontaneous TCC secretion of Th1 cytokines (IL-2, interferon-gamma...

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Autori principali: Weimer, Rolf (Autore) , Zipperle, Silvia (Autore) , Daniel, Volker (Autore) , Zimmermann, Rainer Johannes (Autore) , Schimpf, Klaus (Autore) , Opelz, Gerhard (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: January 1998
In: Clinical & experimental immunology
Year: 1998, Volume: 111, Fascicolo: 1, Pages: 20-29
ISSN:1365-2249
DOI:10.1046/j.1365-2249.1998.00429.x
Accesso online:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1046/j.1365-2249.1998.00429.x
Verlag, lizenzpflichtig, Volltext: https://pmc.ncbi.nlm.nih.gov/articles/PMC1904842/
Testo
Note sull'autore:R. Weimer, S. Zipperle, V. Daniel, R. Zimmermann, K. Schimpf & G. Opelz
Descrizione
Riassunto:To analyse CD4 cell cytokine secretion and helper/suppressor function at a clonal level we established 446 CD4+ T cell clones (TCC) in four healthy controls, three HIV− haemophilia patients, four CDC II,III and four CDC IV patients. Spontaneous TCC secretion of Th1 cytokines (IL-2, interferon-gamma (IFN-γ)) and Th2 cytokines (IL-4, IL-6, IL-10) was determined by ELISA. TCC helper and suppressor functions were tested in a pokeweed mitogen (PWM)-stimulated allogeneic co-culture system using a reverse haemolytic plaque assay for assessment of B cell responses. There was a significant association of TCC surface marker expression (Leu-8, CD45RA) with TCC IL-6 secretion in healthy controls (P < 0·01), HIV− patients (P ≤ 0·001) and CDC II,III patients (P ≤ 0·01) but not in CDC IV patients. Likewise, TCC expression of Leu-8 and CD45RA was significantly associated with TCC suppressor function in healthy controls (P ≤ 0·0005) but not in HIV-infected patients. A reduced TCC helper frequency (≤ 10% of TCC) and an enhanced TCC suppressor frequency (> 80% of TCC) were detected only in those HIV-infected patients who showed an excessively increased TCC IL-6 secretion (> 70% of TCC) together with a significantly diminished TCC IL-10 secretion (≤ 10% of TCC). CD4 cell autoantibodies also were found only in patients with this type of cytokine dysregulation. These data indicate that CD4 cell surface markers lose their functional relevance in HIV-infected patients. HIV-induced IL-6/IL-10 dysregulation of CD4+ T cells, i.e. the up-regulation of spontaneous IL-6 and down-regulation of spontaneous IL-10 secretion, appears to be involved in inducing CD4 helper defects and may promote autoantibody formation against CD4 cells.
Descrizione del documento:Online veröffentlicht: 20. Oktober 2008
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Descrizione fisica:Online Resource
ISSN:1365-2249
DOI:10.1046/j.1365-2249.1998.00429.x