Andy
Senior Member (Voting rights)
Background.
Cytomegalovirus-specific immunoglobulins (CMV-IVIg) can contribute to viral control after transplantation. Apart from neutralizing antiviral activity, knowledge on their potential indirect effects on the restoration of virus-specific T-cell immunity is limited. Therefore, we tested whether CMV-IVIg may affect cytokine induction and proliferation of CMV-specific T cells in vitro.Methods.
Blood samples of 38 individuals (23 kidney transplant recipients and 15 immunocompetent controls) were stimulated using CMV antigens in saturating and low antigen concentration, or with the polyclonal stimulus Staphylococcus aureus enterotoxin B in the presence or absence of CMV-IVIg. CD4 and CD8 T-cell effector function, including the induction of cytokines interferon-gamma, tumor necrosis factor, and interleukin-2, was characterized after 6 h, and specific proliferation was quantified after 5 d using flow cytometry.Results.
Irrespective of antigen concentration, the presence or absence of CMV-IVIg had no effect on the percentage of CMV-specific CD4 and CD8 T cells producing interferon-gamma, tumor necrosis factor, or interleukin-2. However, proliferation of CMV-specific CD3 T cells, including CD4 and CD8 T-cell subpopulations, was significantly higher in the presence of CMV-IVIg at both saturating (P = 0.007) and low antigen concentrations (P = 0.022). In contrast, a lower percentage of both cytokine-producing T cells (P < 0.0001) and proliferating T cells (P < 0.0001) was observed in the presence of CMV-IVIg after polyclonal stimulation.Conclusions.
CMV-IVIg did not have any effect on immediate T-cell effector function. However, the marked effect of CMV-IVIg on increasing the proliferation of CMV-specific T cells while concomitantly reducing polyclonal T-cell function may have implications for the therapeutic use of immunoglobulins to restore CMV-specific T cells in patients with active CMV infection without increasing the alloreactive burden.Open access