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Pathological and Clinical Correlates of FOXP3 + Cells in Renal Allografts during Acute Rejection
Author(s) -
Veronese F.,
Rotman S.,
Smith R. N.,
Pelle T. D.,
Farrell M. L.,
Kawai T.,
Benedict Cosimi A.,
Colvin R. B.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01704.x
Subject(s) - medicine , pathological , graft rejection , pathology , foxp3 , renal transplant , transplantation , immunology , immune system
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.