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1996-02-26
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Document 0112
DOCN M9620112
TI In vitro cytokine treatment of B cell defects in HIV-infected hemophilia
patients.
DT 9602
AU Weimer R; Zipperle S; Daniel V; Opelz G; Department of Transplantation
Immunology, University of; Heidelberg, Germany.
SO Vox Sang. 1995;69(1):27-37. Unique Identifier : AIDSLINE MED/96078298
AB HIV-infected patients exhibit defects in B cell differentiation and in
the IL-6 response of B cells, in association with autoantibody formation
against T cells. These autoantibodies have been implicated as important
factors in the development of immunodeficiency disease. As the
restoration of defective B cell responses might prevent autoantibody
formation and the resulting immunosuppression, we studied whether in
vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4)
or recombinant IL-6 (rIL-6) might restore the response of B cells of
HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4
HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at
CDC stage IV, and 6 healthy controls were tested in Staphylococcus
aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen
(PWM)-stimulated allogeneic B and T cell cocultures. B cell
differentiation was assessed in a reverse hemolytic plaque assay and by
ELISA determination of IgM, IgG and IL-6 in culture supernatants. In
vitro application of rIL-6 resulted in suppression of both elevated
unstimulated and mitogen-stimulated B cell responses in a dose-dependent
manner which was in part due to feedback inhibition. PWM- and
SAC-I-stimulated IgG and IgM responses, respectively, could be restored
after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in
HIV-positive patients. Addition of rIL-4 to cultures resulted in
suppression of both unstimulated and mitogen-stimulated IL-6 secretion
and B cell responses. Severely depressed B cell responses in CDC IV
patients were not significantly affected by cytokine application. These
results indicate that defective Ig responses in HIV-negative patients
may be restored by rIL-2 treatment whereas HIV-induced B cell defects
are not corrected by supply of T cell help or cytokines promoting B cell
growth and differentiation.
DE Autoantibodies/*BIOSYNTHESIS B-Lymphocytes/*DRUG EFFECTS Blood
Coagulation Factors/*ADVERSE EFFECTS Cell Differentiation/DRUG EFFECTS
Cell Division/DRUG EFFECTS Cells, Cultured
Hemophilia/COMPLICATIONS/*DRUG THERAPY/IMMUNOLOGY Human HIV
Infections/*DRUG THERAPY/ETIOLOGY/IMMUNOLOGY Immune Tolerance
Interleukins/*PHARMACOLOGY Pokeweed Mitogens/PHARMACOLOGY Recombinant
Proteins/PHARMACOLOGY Staphylococcus aureus/METABOLISM Stimulation,
Chemical JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).