Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.

Abstract:

BACKGROUND: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.

journal_name

Transplantation

journal_title

Transplantation

authors

Velásquez SY,García LF,Opelz G,Alvarez CM,Süsal C

doi

10.1097/TP.0b013e318296fd69

subject

Has Abstract

pub_date

2013-07-27 00:00:00

pages

154-61

issue

2

eissn

0041-1337

issn

1534-6080

pii

00007890-201307270-00008

journal_volume

96

pub_type

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