title: Spatial differences in the presence of FOXP3+ and GranzymeB+ T cells between the intra- and extravascular compartments in renal allograft vasculopathy.
abstract: BACKGROUND
  Allograft vasculopathy (AV) and native atherosclerosis (NA) share the presence of a T-cell mediated inflammatory response, but differ in overall plaque morphology and growth rate. We studied the distribution and frequency of regulatory- and cytotoxic T cells in the arterial intima lesions in both conditions.
  
  
  RESULTS
  The study is based on vessels of 15 explanted human renal allografts with AV and 10 carotid artery plaques obtained at surgery. Distribution and frequency of cytotoxic- and regulatory T cells, as identified by the expression of Granzyme B (GrB) and FOXP3 was established in NA and AV. Furthermore, we compared the distribution of these cells in AV with the perivascular, interstitial renal tissue using immunohistochemistry. The total number of T cells was much higher in AV than in NA lesions (711±135 and 37±8 CD3/mm(2) respectively, p<0.005, mean, ± SEM). Total numbers of FOXP3(+) regulatory cells were also significantly increased in AV (36±10 and 0.9±0.3 FOXP3(+)/mm(2) p<0.05), but relative numbers, expressed as a percentage of the total number of CD3(+) T cells ((FOXP3(+)/CD3(+)) ×100), were not significantly different (4.6%±0.9 and 2.7%±0.6). GrB(+) cells were rare in NA, but significantly increased numbers of GrB(+) cells were found in AV lesions (85±24 and 0.2±0.1 GrB(+)/mm(2), p<0.05). Perivascular tissues in the allografts showed a higher relative frequency of FOXP3(+) cells than adjacent intimal lesions (14.0%±2.7 and 4.6%±0.9, respectively, p<0.05), but a lower frequency of GrB(+) cytotoxic T cells (16.1%±2.7 and 22.6%±3.6, p<0.05).
  
  
  CONCLUSIONS
  Similar to NA, AV is characterized by a low frequency of intimal FOXP3(+) regulatory T cells. Moreover, significant spatial differences exist in the distribution of functional T cell subsets between the intra- and extravascular micro-environments of the graft.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. o.j.deboer@amc.uva.nl
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Peter
authors.initials: P
authors.lastname: Teeling
authors.forename: Marcel
authors.initials: M
authors.lastname: Jansen
authors.forename: Hanneke
authors.initials: H
authors.lastname: Ploegmakers
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000473:pathology; D001808:Blood Vessels / Q000276:immunology / Q000473:pathology*; D003710:Demography; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology* / Q000276:immunology* / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053804:Granzymes