Natural Killer Cells Were Identified in Human Renal Allograft Rejection
Ping L. Zhang, Sylvia Hayek, Dilip Samarpungavan, Wei Li, Steven R. Cohn, Gampala H. Reddy, Leslie
L. Rocher, Francis Dumler, Raviprasenna K. Parasuraman and Michelle T. Rooney
Departments of Anatomic Pathology, Nephrology, and Transplant Surgery, William Beaumont Hospital,
Royal Oak, MI
Background. Natural killer (NK) cells play an important role in xenograft rejection by way of “natural”
antibody mediated acute humoral xenograft rejection. Because there is a large difference of “natural”
antibodies between two species, and since NK cell inhibitory receptors do not interact well across species
barriers, NK cells become a major mediator for acute humoral xenograft rejection. Theoretically there
may be a greater role for NK cells in xenograft than allograft rejection due to these two mechanisms.
Indeed expression of NK cells in human renal allograft rejection has not been described. We have
evaluated for presence of NK cells by screening CD56 expression, a major receptor of NK cells, in human
renal allograft biopsies (Study 1) and explant specimens (Study 2) from patients with cellular and humoral
rejection.
Design. In Study 1, we compared the CD56 expression in 3 groups of renal transplant biopsies including
1) acute tubular injury as controls, 2) acute cellular rejection (ACR), and 3) antibody mediated rejection
(AMR, also called humoral rejection) with or without ACR. In Study 2, we evaluated CD56 expression in
1) control kidney sections (removed for renal tumors), 2) renal allograft explants with ACR only, and 3)
renal allograft explants with ACR and AMR. All kidney sections were stained for CD56 (monoclonal
antibody from Dako) and their presence in cellular infiltration (CI) area of ACR and peritubular
capillaries (PTC) were counted per high power filed (x400) for comparison using ANOVA.
Results. Control cases stained entirely negative for CD56. In rejection cases, CD56 positive NK cells
represented less than 5% of inflammatory cells in cellular infiltration. Their presence in peritubular
capillaries was also scattered in general (see Table below, *p< 0.05 vs control; #p< 0.05 vs ACR only).
There were no differences in the presence of CD56 positive NK cells between ACR and AMR in two
clinical settings evaluated.
Renal biopsies
Controls
ACR only
AMR
Renal explants
n
CI
PTC
n
CI
PTC
12
13
11
0.00 ± 0.00
3.54 ± 1.36*
0.64 ± 0.31#
0.00 ± 0.00
0.31 ± 0.18
1.28 ± 0.69
10
6
12
0.00 ± 0.00
7.33 ± 3.61*
5.25 ± 1.81*
0.00 ± 0.00
6.17 ± 5.03*
3.92 ± 0.76
Conclusion. According to our knowledge, it is the first human study to show that CD56 positive NK cells
were present in both ACR and AMR, although their amount in both cellular infiltration areas and
peritubular capillaries was small. Further study is needed to determine the significance of NK cells
involved in allograft rejection.