Open AccessHIV‐induced IL‐6/IL‐10 dysregulation of CD4 cells is associated with defective B cell help and autoantibody formation against CD4 cells
Author(s) -
Rolf Weimer,
S. Zipperle,
Volker Daniel,
Rainer Zimmermann,
K. Schimpf,
Gerhard Opelz
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00429.x
Subject(s) - immunology , secretion , cytokine , pokeweed mitogen , autoantibody , medicine , t cell , biology , immune system , antibody , peripheral blood mononuclear cell , in vitro , biochemistry
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.