Mucosal associated invariant T-cells in renal transplant recipients before- and 12 months after transplantation

M.L. Terpstra, M.J. Sinnige, M.C. van Aalderen, E.B.M. Remmerswaal, J. Kers, S.E. Geerlings, F.J. Bemelman

Wednesday 13 march 2019

14:00 - 14:02h at Koningin Máximazaal

Categories: Basaal, Parallelsessie

Parallel session: Parallelsessie III - Basaal I

Background: Mucosal Associated Invariant T (MAIT) cells are innate-like T-cells involved in the antibacterial response by recognizing riboflavin metabolites produced by these organisms and comprise ~10% of the T-cell population in human blood. Bacterial infections are common in renal transplant recipients and MAIT cell functions may be impaired in patients with renal disease. Currently, it is unclear how MAIT cell numbers, phenotype and functions evolve after renal transplantation.

Methods: We used a fluorescently-labelled MR1-tetramer in conjunction with 14-color flowcytometry to identify and characterize MAIT cells in blood from renal transplant recipients obtained pre-transplantation and 12 months post transplantation (n=21) and in healthy controls (n=21).

Results: There was no difference in the absolute number of MAIT cells between the renal transplant recipients (both pre- and post-transplantation) and the controls. Within the MAIT cell population, the amount of CD4^-CD8⁺cells was lower in both the pre- and post-transplantation samples compared to the controls (respectively 70.9%, 73.2% vs. 79.1% p<0.05). However, there was no significant increase in the proportion of CD4^-CD8^-, CD4⁺CD8^-or CD4⁺CD8⁺MAIT cells, neither was there a difference between the pre- and post-transplantation samples.

The mean percentage of MAIT cells expressing CD161, a marker that was previously used to identify MAIT cells, was respectively 88.7%, 94.1% and 92.7% (p>0.05). Thus, without using the MR1 tetramer, about 10% of the MAIT cell population will be missed. Interestingly, CD161^-MAIT cells differed from CD161⁺MAIT cells. Among the CD161^-MAIT cell population, the percentage of cells expressing Tbet, Eomes, Helios (transcription factors) and perforin (cytotoxic potential) was significantly lower, whilst a significant higher percentage of cells expressed Ki67 (proliferation marker) and granzyme B (cytotoxic potential) when compared to CD161⁺MAIT cells. These differences were observed in each patient group.

Furthermore, MAIT cells differed in both pre- and post-transplant samples when compared to the controls with regard to the chemokine receptors CXCR4 and CXCR3, with a higher percentage of MAIT cells expressing CXCR4 (respectively 26.3%, 22.1% vs. 9.5%, p<0.05), and a lower expression of CXCR3 (36.9%, 32.0% vs. 50.0% p<0.05). This suggests a different homing potential for these cells in renal transplant recipients. There was no difference between the pre- and post-transplantation samples.

Conclusions: In contrast to prior reports, MAIT cell numbers are not decreased in the circulation of renal transplant recipients before- and one year after transplantation. About 10 percent of the MAIT cell population appears to be CD161^-and this CD161^-MAIT cell populations displays distinct features. MAIT cells in renal transplant recipient both pre- and post- transplantation express a different homing profile. Further research is warranted to determine what the cause and consequence is of this altered expression of chemokine receptors.