Dendritic Cells Enriched from Swine Thymus Co‐express CD1, CD2 and Major Histocompatibility Complex Class II and Actively Stimulate Alloreactive T Lymphocytes

Abstract

Initial characterization and partial purification of thymic dendritic cells (DC) from miniature swine were carried out with the ultimate goal of using these cells to induce transplantation tolerance in this preclinical animal model. Immunohistochemical analysis of swine thymic tissue sections has shown DC to be large cells located in the medullary and the cortico-medullary regions as evidenced by the presence of surrounding Hassal bodies. These cells exhibit membrane processes and express the CD1, granulocyte/macrophage (G/M), and major histocompatibility complex (MHC) class II surface antigens, as well as the S100 cytosolic and nuclear markers found in humans to be specific for DC. Dendritic cells were purified from thymi following collagenase treatment, Percoll gradient centrifugation, and adhesion steps to plastic. Cells similar in morphology and phenotype to those described in tissue sections were detected in the lighter density layers of the gradient and represented 0.02% of the starting cell number. Removal of plastic nonadherent cells showed enrichment levels similar to those reported for murine and human DC. Two-colour flow cytometric analysis of purified pig DC identified these cells as MHC class IIhi, CD1+, CD2+, and G/M+. The dendritic nature of these cells was confirmed by their potent ability to stimulate alloreactive T lymphocytes. Modification of porcine thymic DC by transfer of allogeneic MHC genes and reinjection into the DC donor should permit testing of the role of this DC subset in the induction of transplantation tolerance.

Site‐specific expression of CD11b and SIRPα (CD172a) on dendritic cells: implications for their migration patterns in the gut immune system

“…Further research is necessary to determine whether porcine SIRPa + and SIRPa -DC have similar functional differences. Previous studies in pigs have described SIRPa + DC in skin, peripheral blood, thymus, and intestinal LP [23,27,38,39], and SIRPa -DC in PP and, as natural interferon-producing cells, in different regions of the intestinal mucosa [32,40]. In our study, SIRPa + and SIRPa -DC were detected in all the compartments examined, but their frequency differed greatly: In "peripheral" regions where antigen uptake occurs, i.e.…”

Porcine peripheral blood dendritic cells and natural interferon‐producing cells

“…From previous work, it was known that the SWC3 molecule was dominant on myeloid cells 31–33 . In addition, porcine monocyte‐derived DC, bone marrow‐derived DC, 22 lamina propria DC, 34 dermal DC 35 and thymic DC 36 all express SWC3. Consequently, it was assumed as a working hypothesis that blood DC should also express SWC3.…”

“…Human blood DC circulate in an immature state, and were thus also termed pre‐DC. After culture, particularly in the presence of appropriate signals, a rapid maturation to fully active APC is induced 36,37 . The existence of this phenomenon with putative porcine blood DC was tested by comparative analysis of MHC class II and CD80/86 as maturation markers.…”

Membrane markers of the immune cells in swine: an update

“…One gene, a class I-like protein, with a 40 kDa heavy chain and a 12 kDa light chain [86], thus highly similar to human CD1a [55]. In both humans and pigs, CD1 group I (CD1 a, b and c) markers are expressed on cortical thymocytes, a fraction of B cells, thymic dendritic cells, some macrophages and Langerhans cells [147,167,183].…”