Identification of the Cellular Subpopulations Infiltrating Rejecting Cadaver Renal Allografts

Hall, Bruce M.; Bishop, G. Alex; Farnsworth, Annabelle; Duggin, Geoffrey G.; Horvath, J. S.; Sheil, A. G. R.; Tiller, D. J.

doi:10.1097/00007890-198406000-00008

Cited by 38 publications

(12 citation statements)

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“…12,13,33 During renal allograft rejection, the number of infiltrating CD3-positive T cells and CD68-positive macrophages increases, consistent with previous studies. 6,7,34 CD3-positive T cells were diffusely distributed in the renal interstitium and at times formed nodular aggregates, typically localized adjacent to large veins. The increased number of T cells infiltrating the renal allograft has been reported to be caused by both CD4-and CD8-positive subpopulations, 6,7,34 and a correlation between the distribution pattern and T-cell subset has been described 6,34,35 (ie, areas of T-cell aggregates consist mainly of CD4-positive T cells, whereas CD8-positive T cells diffusely infiltrate the interstitium).…”

Section: Discussionmentioning

confidence: 99%

“…6,7,34 CD3-positive T cells were diffusely distributed in the renal interstitium and at times formed nodular aggregates, typically localized adjacent to large veins. The increased number of T cells infiltrating the renal allograft has been reported to be caused by both CD4-and CD8-positive subpopulations, 6,7,34 and a correlation between the distribution pattern and T-cell subset has been described 6,34,35 (ie, areas of T-cell aggregates consist mainly of CD4-positive T cells, whereas CD8-positive T cells diffusely infiltrate the interstitium). CD3-positive T cells and macrophages are the main cell types infiltrating the subendothelial space during vascular rejection.…”

Section: Discussionmentioning

confidence: 99%

“…3, 4 The main types of infiltrating cells are subsets of T cells and macrophages at different stages of activation. [5][6][7] Distinct immune responses against different challenges are termed T helper subtype 1 (Th1)-like or Th2-like according to the classes of Th cells involved. 8, 9 These subtypes of Th cells are characterized by the expression patterns of cytokines and chemokine receptors.…”

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Expression of chemokines and chemokine receptors during human renal transplant rejection

Segerer

Chen

Eitner

et al. 2001

American Journal of Kidney Diseases

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• Infiltration of renal allografts by leukocytes is a hallmark of acute transplant rejection. Chemokines attract leukocytes bearing specific chemokine receptors, and the specific leukocyte chemokine receptor phenotype is associated with types of immune responses, ie, T helper subtype 1 (Th1; CXC chemokine receptor 3 [CXCR3], CC chemokine receptor 5 [CCR5]) versus Th2 (CCR3, CCR4, CCR8). We studied the expression of the chemokine monocyte chemoattractant protein-1 and the chemokine receptors CCR2B and CXCR4 messenger RNA (mRNA) by in situ hybridization, as well as the chemokine receptors Duffy antigen receptor for chemokines (DARC) and CCR5 protein by immunohistochemistry in renal biopsy specimens with acute cellular rejection (n ‫؍‬ 12) and acute vascular rejection (n ‫؍‬ 8), transplant nephrectomy specimens (n ‫؍‬ 6), and normal areas of tumor nephrectomy specimens (n ‫؍‬ 5). CC chemokines and CC chemokine receptor mRNA expression were evaluated by ribonuclease protection assay in specimens from four transplant nephrectomies and one tumor nephrectomy. Upregulation of mRNAs for the chemokines, interferon-inducible protein-10 (IP-10); regulated on activation normal T-cell expressed and secreted; macrophage inflammatory protein-1␣ (MIP-1␣); MIP-1␤; and lymphotactin, as well as the chemokine receptors, CCR2 and CCR5, were documented during allograft rejection. CCR1 mRNA was detectable in both allografts and controls, but CCR3 and CCR8 were absent. The number of CXCR4, CCR5, and CCR2B mRNAs expressing leukocytes and DARC-positive vessels increased during rejection episodes. CXCR4 mRNA was the most widely expressed. Leukocytes in diffuse interstitial infiltrates were mainly CCR5 positive, but in areas in which leukocytes formed nodular aggregates of infiltrating cells, the number of CCR5-positive cells was low. Instead, leukocytes in these nodular aggregates mainly expressed CXCR4. DARC was expressed on peritubular capillaries, where it was upregulated in areas of interstitial infiltration. Induction of chemokines during renal allograft rejection is accompanied by infiltration of leukocytes bearing the respective chemokine receptors. The upregulation of the CXCR3 ligand IP-10, as well as CCR5 and its ligands, in the absence of CCR3 and CCR8 is indicative that renal allograft rejection is primarily the result of a Th1-type immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of chemokines and chemokine receptors during human renal transplant rejection

Segerer

Chen

Eitner

et al. 2001

American Journal of Kidney Diseases

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“…The classical acute graft rejection is characterized by an invasion of mononuclear cells, predominately immature lymphocytes, plasma cells, and macrophages (Hall et al 1984). These criteria for graft rejection were not present.…”

Section: Discussionmentioning

confidence: 99%

Long‐term outcome of RPE allografts to the subretinal space of rabbits

Crafoord¹,

Algvere²,

Seregard³

et al. 1999

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To determine the long-term RPE allograft survival in the subretinal space using suspensions of RPE cells and atraumatic transplantation surgery. Methods: Nineteen albino rabbits were transplanted with suspensions of pigmented RPE cells from brown rabbits. Following pars plana vitrectomy, the RPE cell suspension was injected through a small retinotomy using a glass micropipette into the subretinal space under microscopic control. No immunosuppression was used. The eyes were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy, using monoclonal antibodies for identifying macrophages. Results: Transplanted RPE cells were present in the subretinal space in all eyes at 6 months. There was no fluorescein leakage. Generally, the RPE allograft formed a monolayer, but focal fragmentation and disruption with dispersion of melanin pigment occurred. Foci of multilayers of cells in the subretinal space, containing large macrophages, were associated with adjacent photoreceptor damage. There was no infiltration of lymphocytes but macrophages and glial cells were contiguous to the transplant. Cells harboring intracytoplasmatic melanin pigment were observed in the neural retina. Conclusion: Transplantation of RPE cell suspensions to the subretinal space generally forms a monolayer that persists at 6 months. However, in areas of multilayers of RPE cells and macrophages, graft failure occurs in combination with adjacent photoreceptor damage. Graft failure is not associated with the infiltration of lymphocytes, but other mechanisms seem to occur.

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“…Transcript expression is highly altered in rejection (1,(14)(15)(16)(17) and provides an objective and quantitative measurement of events in the graft without the need for arbitrary thresholds. Expression of a pathogenesis-based transcript (PBTs) sets associated with inflammatory cells allows a robust and objective estimation of the inflammatory disturbance in allografts (18)(19)(20). Analogous to previously defined cytotoxic T-cell-associated transcripts (QCATs), which reflect the T-cell burden in the graft, the present study defined a set of B-cell-associated transcripts (BATs) and a set of immunoglobulin associated transcripts (IGTs) to assess the burden of B cells and plasma cells in human renal allograft biopsies taken for clinical indication.…”

Section: T-cell-mediated Rejection (Tcmr) With Dense Cd20mentioning

confidence: 99%

Expression of B Cell and Immunoglobulin Transcripts Is a Feature of Inflammation in Late Allografts

Einecke

Reeve

Mengel

et al. 2008

American Journal of Transplantation

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Identification of the Cellular Subpopulations Infiltrating Rejecting Cadaver Renal Allografts

Cited by 38 publications

References 0 publications

Expression of chemokines and chemokine receptors during human renal transplant rejection

Expression of chemokines and chemokine receptors during human renal transplant rejection

Long‐term outcome of RPE allografts to the subretinal space of rabbits

Expression of B Cell and Immunoglobulin Transcripts Is a Feature of Inflammation in Late Allografts

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