1. Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.
- Author
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Velásquez SY, García LF, Opelz G, Alvarez CM, and Süsal C
- Subjects
- ADAM Proteins immunology, ADAM10 Protein, ADAM17 Protein, Adult, Amyloid Precursor Protein Secretases immunology, Female, Flow Cytometry, Humans, Immunophenotyping, Isoantigens immunology, Ki-1 Antigen blood, Kidney Transplantation immunology, Lymphocyte Activation immunology, Male, Membrane Proteins immunology, Middle Aged, Solubility, Up-Regulation immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Immunologic Memory immunology, Interferon-gamma immunology, Interleukin-2 immunology, Ki-1 Antigen immunology
- 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.
- Published
- 2013
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