"Neutral allografts"--lack of allogeneic stimulation by cultured human cells expressing MHC class I and class II antigens.
Cultured human dermal fibroblasts, smooth muscle cells, epidermal cells and endothelial cells were tested for immunogenicity in an in vitro allostimulation assay. Gamma interferon was used to induce MHC class II expression, since these cells constitutively express class I but not class II antigens. In contrast to human dermal fibroblasts, smooth muscle cells and epidermal cells, endothelial cells, were able to stimulate a significant proliferative response in normal allogeneic lymphocytes. Since ICAM-1 was also expressed on these cells, this inability to initiate allostimulation was probably not due to the absence of adhesion molecules. Addition of exogenous cytokines such as IL-1, IL-2, and TNF did not restore T cell proliferation in the test system. Therefore the inability of dermal fibroblasts, smooth muscle cells, and epidermal cells to initiate significant allostimulation was also not due to lack of cytokine production. It appears that certain cells lack as-yet-undefined costimulatory factors required for their effective recognition as foreign. These results support the notion that cultured human fibroblasts, smooth muscle cells, and epidermal cells could serve as building blocks of engineered "neutral allografts" for use across MHC barriers.
Theobald
V A
VA
Organogenesis Inc., Cambridge, Massachusetts 02142.
Lauer
J D
JD
Kaplan
F A
FA
Baker
K B
KB
Rosenberg
M
M
D016525:Antigenic Modulation / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007213:Indomethacin