T-cell inhibitory capacity of hyperimmunoglobulins is influenced by the production process.
Intravenous immunoglobulin (IVIg) preparations are widely used for anti-inflammatory therapy of autoimmune and systemic inflammatory diseases. Hyperimmunoglobulins enriched in neutralizing antibodies against viruses can, in addition to their virus-neutralizing activity, also exert immunomodulatory activity. Previously, we observed that Cytotect®, an anti-CMV hyperimmunoglobulin, was less effective in suppressing human T-cell responses in vitro compared to Hepatect® CP, an anti-HBV hyperimmunoglobulin. We hypothesized that the poor immunomodulatory activity of Cytotect® results from treatment with β-propiolactone during the manufacturing process. The manufacturer of these hyperimmunoglobulins has now introduced a new anti-CMV hyperimmunoglobulin, called Cytotect® CP, in which β-propiolactone treatment is omitted. Here we show that Cytotect® CP inhibits PHA-driven T-cell proliferation and cytokine production with similar efficacy as Hepatect® CP, whereas the former Cytotect® does not. In addition, Cytotect® CP inhibits allogeneic T-cell responses better than Cytotect®. Our results advocate the use of hyperimmunoglobulins that have not been exposed to β-propiolactone in order to benefit from their immunomodulatory properties.
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands.
Rogier
R
van Gent
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands.
Haziz
H
Jaadar
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands.
Angela S W
AS
Tjon
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands.
Shanta
S
Mancham
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands. Electronic address: j.kwekkeboom@erasmusmc.nl.
Jaap
J
Kwekkeboom
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology*; D016756:Immunoglobulins, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011420:Propiolactone; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D010835:Phytohemagglutinins; C045781:cytomegalovirus-specific hyperimmune globulin; D011420:Propiolactone; D007371:Interferon-gamma
Hyperimmunoglobulin; Immunomodulation; Intravenous immunoglobulin; T-cell responses; β-propiolactone