Peripheral T cell activation in long-term renal transplant patients: concordant upregulation of adhesion molecules and cytokine gene transcription.

In renal transplant, patients, the number of T cells expressing high levels of LFA-1 (LFA-1-bright) and of T cells expressing CD57 increases in response to viral infection, even if the latter is asymptomatic. Their role in long-term renal transplant patients with cytomegalovirus (CMV) antigenemia and concomitant transplant dysfunction was investigated. For this purpose, this study used triple-color flow cytometry, fluorescence-activated cell sorting of peripheral blood T cells (CD3+/LFA-1-dim or -bright and CD8+/CD57+ or CD57- subsets), and subsequent semiquantitative reverse transcription-polymerase chain reaction. Cytokine mRNA levels for interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, tumor necrosis factor alpha, and interferon-gamma, as well as Granzyme A and IL-2R p55 and p75 transcripts were determined and compared in peripheral blood mononuclear cells and in separated T cell subsets. Although in patients with CMV infection and/or rejection, cytokine transcripts were readily detected and the levels in the CD3+/LFA-1-bright subsets were, by orders of magnitudes, higher than in the LFA-1-dim subset, hardly any cytokine message was found in patients without CMV infection or rejection episodes or in control subjects. The expression of Granzyme A, which is involved in cytotoxic T lymphocyte-mediated cytotoxicity, was not upregulated in LFA-1-bright T cells, which is in discordance with cytokine levels. Differences between CD57+ and CD57- T cells were limited to the IL-2R p55 mRNA, of which the former expressed significantly less than the latter. It is concluded that upon virus-induced activation of peripheral blood T cells, an effector type that is marked by high inflammatory but small cytotoxic potential is produced. The results of this study propose that these cells represent a correlate of persistent immune activation and are liable to produce graft dysfunction, although they are unable to clear the organism from virus infection because of their lack of cytotoxic potential.

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CYTOMEGALOVIRUS (CMV)-SPECIFIC CD4 AND CD8 T CELL RESPONSE TO CMV INFECTION IN RENAL TRANSPLANT PATIENTS.

Transplantation Journal ◽

10.1097/00007890-200607152-00597 ◽

2006 ◽

Vol 82 (Suppl 2) ◽

pp. 268-269

Author(s):

&NA;

Keyword(s):

T Cell ◽

Renal Transplant ◽

Cell Response ◽

Cd8 T Cell ◽

T Cell Response ◽

Cmv Infection ◽

Transplant Patients ◽

Renal Transplant Patients

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SP732INCREASED EXPRESSION OF THE COINHIBITORS PD-1 AND BTLA ON CMV-SPECIFIC T-CELLS IS ASSOCIATED WITH SYMPTOMATIC CMV INFECTION IN RENAL TRANSPLANT PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy104.sp732 ◽

2018 ◽

Vol 33 (suppl_1) ◽

pp. i594-i594

Author(s):

Ming Sun ◽

Sebastian Dolff ◽

Andreas Kribben ◽

Anja Gaeckler ◽

Hana Rohn ◽

...

Keyword(s):

T Cells ◽

Renal Transplant ◽

Cmv Infection ◽

Transplant Patients ◽

Renal Transplant Patients

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Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

International Journal of Molecular Sciences ◽

10.3390/ijms20092194 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2194 ◽

Cited By ~ 8

Author(s):

Hung-Chih Lai ◽

Ji-Fan Lin ◽

Thomas I.S. Hwang ◽

Ya-Fang Liu ◽

An-Hang Yang ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Renal Transplant ◽

Programmed Cell Death ◽

Advanced Cancer ◽

Advanced Malignancy ◽

Transplant Patients ◽

Programmed Cell Death 1 ◽

Renal Transplant Patients

Given advancements in cancer immunity, cancer treatment has gained breakthrough developments. Immune checkpoint inhibitors, such as programmed cell death 1 (PD-1) inhibitors, are the most promising drugs in the field and have been approved to treat various types of cancer, such as metastatic melanoma, head and neck squamous cell carcinoma, and urothelial carcinoma. However, whether PD-1 inhibitors should be administered to renal transplant patients with advanced cancer remains unclear because the T-cells produced after administration of these inhibitors act against not only tumor antigens but also donor alloantigens. Thus, the use of PD-1 inhibitors in kidney-transplanted patients with advanced cancer is limited on account of the high risk of graft failure due to acute rejection. Hence, finding optimal treatment regimens to enhance the tumor-specific T-cell response and decrease T-cell-mediated alloreactivity after administration of a PD-1 inhibitor is necessary. Thus far, no recommendations for the use of PD-1 inhibitors to treat cancer in renal transplant patients are yet available, and very few cases reporting kidney-transplanted patients treated with PD-1 inhibitors are available in the literature. Therefore, in this work, we review the published cases and suggest feasible approaches for renal transplant patients with advanced malignancy treated by a PD-1 inhibitor. Of the 22 cases we obtained, four patients maintained intact grafts without tumor progression after treatment with a PD-1 inhibitor. Among these patients, one maintained steroid dose before initiation of anti-PD1, two received immunosuppressive regimens with low-dose steroid and calcineurin inhibitor (CNI)-elimination with sirolimus before initiation of anti-PD-1 therapy, and one received combined anti-PD-1, anti-vascular endothelial growth factor (VEGF), and chemotherapy with unchanged immunosuppressive regimens. mammalian target of rapamycin (mTOR) inhibitors and anti-VEGF may act as regulators of tumor-specific and allogenic T-cells. However, more studies are necessary to explore the optimal therapy and ensure the safety and efficacy of PD-1 inhibitors in kidney-transplanted patients.

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