Immune evasion by neocartilage-derived chondrocytes: Implications for biologic repair of joint articular cartilage.
Degeneration of joint articular cartilage is a leading cause of disability worldwide, and is due in large part to the fact that adult articular cartilage is unable to undergo effective intrinsic repair. To overcome this barrier, we have developed a tissue engineering strategy which harnesses the superior anabolic activity of juvenile chondrocytes to produce a scaffold-independent, living neocartilage graft. Preclinical studies demonstrate that bioengineered neocartilage survives allogeneic and xenogeneic transplantation, suggesting the utility of universal donor-derived neocartilage for joint repair. However, the mechanism underlying neocartilage transplant tolerance remains poorly understood. We show here that neocartilage-derived chondrocytes are unable to stimulate allogeneic T cells in vitro, and they do not constitutively express cell surface molecules required for induction of T cell immune responses, including major histocompatibility complex (MHC) Class II antigens and costimulatory molecules B7-1 and B7-2. Additionally, chondrocytes suppress, in a contact-dependent manner, the proliferation of activated T cells, with suppression associated with chondrocyte expression of multiple negative regulators of immune responses, including B7 family members (B7-H1, B7-DC, B7-H2, B7-H3, and B7-H4), chondromodulin-I and indoleamine 2,3-dioxygenase. Thus, the survival of transplanted bioengineered neocartilage may depend on both passive and active mechanisms of immune evasion.
Adkisson
H D
HD
ISTO Technologies, Inc., 1155 Olivette Executive Parkway, St. Louis, MO 63132, USA. dadkisson@istotech.com
Milliman
C
C
Zhang
X
X
Mauch
K
K
Maziarz
R T
RT
Streeter
P R
PR
D000293:Adolescent; D000328:Adult; D000818:Animals; D002356:Cartilage / Q000637:transplantation; D002358:Cartilage, Articular / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D019902:Chondrocytes / Q000166:cytology* / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
D000949:Histocompatibility Antigens Class II