Characterization of cutaneous antigen presentation in partially inbred miniature swine

Abstract

MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (APC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8-4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function, EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coated petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 x 10(7) TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous APC which are able to induce cutaneous immunity in a matter similar to Langerhans cells in murine or human skin.

Langerhans cells in porcine skin

“…LCs have also been described in domestic animals including pigs, cattle, sheep, dogs, cats and chickens (Hollis and Lyne, 1972;Khalil et al, 1982;Marchal et al, 1995;Perez-Torres and Ustarroz-Cano, 2001;Romano and Balaguer, 1991). The description of porcine LCs is, however, based on the microscopic identification of BGs in epidermal DCs (Grabbe et al, 1994;Monteiro-Riviere, 1992;Romano and Balaguer, 1991) and LC-like cells derived from monocytes (Paillot et al, 2001). Conversely, we and others did not observe these granules in porcine skin and skin-derived DCs (Bautista et al, 2002;Gregg et al, 1995a).…”

“…Knowledge of the role of LCs in porcine immunity is critical to achieving this understanding. Grabbe et al (1994) showed that inbred miniature pigs possess skin APCs which function in the same way as human and murine LCs. In addition, other studies have shown that porcine skin DCs are important in delayed hypersensitivity reactions (Grabbe et al, 1994;McFarlin and Balfour, 1973) and are involved in allergic contact dermatitis (Vana and Meingassner, 2000).…”

“…Grabbe et al (1994) showed that inbred miniature pigs possess skin APCs which function in the same way as human and murine LCs. In addition, other studies have shown that porcine skin DCs are important in delayed hypersensitivity reactions (Grabbe et al, 1994;McFarlin and Balfour, 1973) and are involved in allergic contact dermatitis (Vana and Meingassner, 2000). Our data show that porcine skin DCs transcribe CD207/langerin mRNA and express langerin protein, which is reactive with antibodies raised against human langerin and that the majority of DCs in porcine skin epithelium are LCs.…”

Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model

“…Pig skin shares strong histological similarities with human skin, such as low hairiness, thick strateum corneum with similar lipid composition [13], and dermis structure [14]. CD207 high LC have been identified in pig epidermis [15], [16], [17]. In addition, pig DC that had migrated from skin explants expressed CD1, CD172a, MHC-II and CD80/CD86 [15].…”

Minipigs in Translational Immunosafety Sciences

“…Although remarkable similarities of porcine and human skin structures have been known for a long time, skin immunology and its key players such as dermal DC (DDC)-which play a central role as antigen presenting cells (APC)-are just beginning to be explored in detail in porcine skin (Summerfield, Auray, and Ricklin 2015;Summerfield, Meurens, and Ricklin 2015). MHC class II-positive cells with morphology and skin density similar to APC in man were described in miniature pig skin (Grabbe et al 1994). These cells were able to both stimulate allogeneic T cell proliferation and trigger a delayed type hypersensitivity response (Grabbe et al 1994).…”