Characterisation of Tertiary Lymphoid Organs in Explanted Rejected Donor Kidneys.
PURPOSE
Tertiary lymphoid organs (TLOs) have been described within organ allografts, but whether they promote destructive or beneficial alloimmune responses remains controversial. This study aimed to characterize TLO distribution in human chronically rejected renal allografts and to explore their functions.


METHODS
A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry. Correlations between lymphoid neogenesis and the expression of IL-17, IL-21, C4d, podoplanin, IL-10, and Foxp3 were evaluated. In addition, the duration of graft function was compared between allografts that harbored or lacked TLOs.


RESULTS
TLOs were detected in 27.6% of chronically rejected renal grafts, but they rarely had germinal centers. Lymphoid neogenesis negatively correlated with CXCR5 expression, and almost completely correlated with IL-17 expression. Those grafts that harbored a TLO functioned for an average of 5.98 years and those without a TLO lasted only about half as long with an average of 2.91 years. However, in grafts that harbored a TLO, Foxp3(+) cells were comparitively less than those without a TLO. Foxp3(+)CXCR5(+) Tfr cells and IL-10(+) cells were rare in grafts, irrespective of the presence of a TLO.


CONCLUSION
TLOs in chronically rejected kidney allografts may be an epiphenomenon of the inflammatory process that is related to graft duration.
['Xu|Xiaoguang|X|', 'Han|Yong|Y|', 'Wang|Qiang|Q|', 'Cai|Ming|M|', 'Qian|Yeyong|Y|', 'Wang|Xinying|X|', 'Huang|Haiyan|H|', 'Xu|Liang|L|', 'Xiao|Li|L|', 'Shi|Bingyi|B|']
D000328:Adult D015415:Biomarkers D049109:Cell Proliferation D005260:Female D051858:Forkhead Transcription Factors D015870:Gene Expression D018858:Germinal Center D006084:Graft Rejection D006680:HLA Antigens D006801:Humans D007150:Immunohistochemistry D016753:Interleukin-10 D020381:Interleukin-17 D016030:Kidney Transplantation D008221:Lymphoid Tissue D008297:Male D008875:Middle Aged D054380:Receptors, CXCR5 D014184:Transplantation, Homologous
tertiary lymphoid organ lymphoid neogenesis Chronic allograft rejection kidney transplantation