Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitro.
BACKGROUND
Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms.


RESULTS
CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFNgamma), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and FcgammaRIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions.


CONCLUSIONS
We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response.
Hoetzenecker
K
K
Department of Surgery, Medical University of Vienna, Austria.
Hacker
S
S
Hoetzenecker
W
W
Sadeghi
K
K
Sachet
M
M
Pollreisz
A
A
Mangold
A
A
Wliszczak
T
T
Bielek
E
E
Muehlbacher
F
F
Klepetko
W
W
Ankersmit
H J
HJ
D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D016756:Immunoglobulins, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology
D017252:CD3 Complex; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; C045781:cytomegalovirus-specific hyperimmune globulin; D016753:Interleukin-10; D007371:Interferon-gamma