Ultra-localization of Foxp3+ T cells within renal allografts shows infiltration of tubules mimicking rejection.
Kidney transplant recipients are monitored for rejection by measurement of serum creatinine and graft biopsies. Biopsy samples are evaluated according to the Banff classification, which states that infiltration of tubules by mononuclear cells is an indicator of acute rejection. However, regulatory T cells play a crucial role in the overall immune response and are also present within transplanted tissue. We hypothesize that infiltration of mononuclear cells within kidney grafts is not always associated with rejection, especially if a high proportion of this infiltrate is regulatory T cells. Using a life-sustaining mouse kidney transplant model, we found that mononuclear cell tubular infiltration can occur in both rejecting and tolerant grafts. However, tolerant kidney grafts demonstrated a higher and sustained level of Foxp3+ regulatory cells. Importantly, a significant proportion of these cells were found within tubules. In cases in which graft function was normal, these cells were not harmful to the kidney and could be said to be mimicking, rather than causing, rejection.
Brown
Kathryn
K
Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's, King's Hospital, London SE1 9RT, UK.
Moxham
Victoria
V
Karegli
Julieta
J
Phillips
Richard
R
Sacks
Steven H
SH
Wong
Wilson
W
D000818:Animals; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006183:H-2 Antigens; D053645:Interleukin-2 Receptor alpha Subunit