In Vivo Recognition by the Host Adaptive Immune System of Microencapsulated Xenogeneic Cells
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BACKGROUND: Microencapsulation is under consideration as a means of enabling pancreatic islet transplantation. To understand better the ongoing destructive host response, we examined whether the adaptive immune system of the recipient recognized polymer-encapsulated xenogeneic cells implanted intraperitoneally. METHODS: Balb/c mice were implanted with xenogeneic Chinese hamster ovary cells, inside and outside poly(hydroxyethyl methacrylate-methyl methacrylate) microcapsules, and responses were compared with xenografted Chinese hamster skin (positive control). Capsules were localized within an agarose rod. Splenocyte proliferation upon rechallenge in vitro, antibody titer in serum, and Th1/2 polarization (assessed by interleukin-4 and interferon-gamma in supernatants of antigen-challenged splenocytes and immunoglobulin [Ig]G1 and IgG2a antibody isotypes in serum) were measured. RESULTS: Encapsulation did not prevent a strong recipient antibody response. Splenocyte proliferation in vitro did not differ after priming by implanted cells, inside or outside capsules. Thus, the capsule membrane did not prevent indirect recognition of shed antigens. However, after 10 days of implantation, proliferation was lower than that induced by skin grafts, although this difference disappeared by 2 months. This transient T-cell suppression was unexpected because encapsulated cell viability was already compromised by 10 days. The influence of Th1/2 bias did not explain the observed suppression. Cells inside capsules elicited a consistent Th2 response, whereas cells outside capsules elicited a mixed response, and skin xenografts showed an initial Th2 response that became mixed by 2 months. CONCLUSIONS: Encapsulation does not prevent host immune responses, but the inflammatory response to the implanted biomaterials or xenogeneic cells may be responsible both for encapsulated cell death and transient T-cell suppression.
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