Release of Soluble CD30 After Allogeneic Stimulation Is Mediated by Memory T Cells and Regulated by IFN-γ and IL-2
Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation.Methods
We investigated the kinetics of CD30 expression on CD4+ and CD8+ T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3+ lymphocytes were evaluated in dialysis patients and matched controls.Results
Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4+ cells (P<0.001 at 96 hr) and effector CD8+ cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (P<0.001) and interleukin (IL)-2 (P<0.001) impaired the release of sCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls.Conclusions
Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4+ as well as CD8+ memory T cells and increased release of sCD30 from these cells in an IFN-γ– and IL-2–dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ– and IL-2–producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.