Spatial differences in the presence of FOXP3+ and GranzymeB+ T cells between the intra- and extravascular compartments in renal allograft vasculopathy

• Published in: PloS one Vol. 6; no. 4; p. e18656
• Main Authors: de Boer, Onno J, Teeling, Peter, Jansen, Marcel, Ploegmakers, Hanneke, van der Loos, Chris M, Kummer, J Alain, Florquin, Sandrine, van der Wal, Allard C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.04.2011; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Allografts; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - pathology; Blood vessels; Blood Vessels - immunology; Blood Vessels - pathology; Cardiovascular disease; Carotid arteries; Carotid artery; CD3 antigen; Cloning; Compartments; Coronary vessels; Cytology; Cytotoxicity; Demography; Ethics; Extracellular matrix; Female; Forkhead Transcription Factors - metabolism; Foxp3 protein; Granzyme B; Granzymes - metabolism; Growth rate; Heart; Humans; Immunohistochemistry; Immunoregulation; Inflammation; Inflammatory response; Kidney transplantation; Kidney Transplantation - adverse effects; Kidneys; Laboratories; Lesions; Lipids; Lymphocyte Count; Lymphocyte Subsets - pathology; Lymphocytes; Lymphocytes T; Male; Medicine; Middle Aged; Nephrectomy; Pathogenesis; Pathology; Phosphatase; Plaques; Review boards; Rheumatoid arthritis; Rheumatology; Skin diseases; Spatial distribution; Surgery; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - pathology; T-Lymphocytes, Regulatory - pathology; Tissues; Transplantation, Homologous; Transplants & implants; Vascular diseases; Vascular Diseases - etiology; Vascular Diseases - immunology; Vascular Diseases - pathology; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018656

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. 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). 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.