Donor-specific memory T cell responsiveness decreases after kidney trans¬plantation

A. Mendoza, D. Reijerkerk, R. de Kuiper, T. van Gelder, D.A. Hesselink, C.C. Baan, N.M. van Besouw

Thursday 14 march 2019

11:40 - 11:50h at Tropentheater

Categories: Best abstracts, Parallelsessie

Parallel session: Parallelsessie XII – Best abstracts III

Background: High numbers of donor-reactive IFN-γand IL-21 producing peripheral blood mononuclear cells (PBMCs) pre transplantation have been shown to be associated with early acute rejection. However, knowledge about the presence of these cytokine producing cells in patients more than 1 year after transplantation is lacking. In the present study, we investigated the frequency of donor-specific IL-21 and IFN-γproducing cells in renal transplant patients prior to transplantation until 5-7 years after transplantation.

Methods: PBMC samples from 44 kidney transplant patients were obtained pre transplantation, at 1 year and at 5-7 years after transplantation. The frequency of IL-21 and IFN-γproducing PBMCs was analyzed by enzyme-linked immunospot assay (Elispot). Patient PBMC were stimulated with irradiated donor or third-party cells, which were completely HLA-mismatched with donor and recipient. Unstimulated patient PBMCserved as negative control. Stimulation with a cocktail of peptides to influenza, CMV and EBV (ICE) and staphylococcal enterotoxin B (SEB) served as positive control for the HLA class I and class II response, respectively.

Results: The number of donor-reactive IL-21 and IFN-γproducing PBMCs was lower at 1 year compared to pre transplantation [median and interquartile range: 22/3x10⁵PBMC (10-57) vs. 6/3x10⁵PBMC (4-16), p<0.0001] and 26/1x10⁵PBMC (12-51) vs. 7/1x10⁵PBMC (5-17), p=0.002, respectively]. This difference with pre-transplantation samples was also significant in samples obtained 5-7 years post transplantation [22/3x10⁵PBMC (10-57) vs. 11/3x10⁵PBMC (5-25), p<0.0001] and 26/1x10⁵PBMC (12-51) vs. 11/1x10⁵PBMC (5-26), p=0.009, respectively]. In contrast, the response against 3^rd-party cells, ICE and SEB remained stable over time. 

Conclusions: Our data suggest that donor-specific hypo-responsiveness is present at 1 year after kidney transplantation and can still be demonstrated 5-7 years later. At the same time, anti 3^rd-party immunity and responses to antigens presented by HLA class I and class II are maintained. This could imply that allograft tolerance might occur from one year after transplantation onwards. A better understanding of the mechanisms underlying allograft tolerance could help overcome chronic rejections and immunosuppressive side effects.