Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.
The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p < 0.01). Most FOXP3(+) cells were CD4(+) (96%); a minority expressed CD8. FOXP3(+)CD4(+) cells were concentrated in the tubules (p < 0.001), suggesting a selective attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined.
Veronese
F
F
Pathology and Surgical Services, Massachusetts General Hospital, Boston, Massachusetts, USA.
Rotman
S
S
Smith
R N
RN
Pelle
T D
TD
Farrell
M L
ML
Kawai
T
T
Benedict Cosimi
A
A
Colvin
R B
RB
D015703:Antigens, CD / Q000032:analysis; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous / Q000473:pathology; D016896:Treatment Outcome
D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger