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Early up‐regulation of CXC‐chemokine expression is associated with strong cellular immune responses to murine skin xenografts
Author(s) -
Lee Eun Mi,
Park Joon Oh,
Kim Donghee,
Kim Jae Young,
Oh KookHwan,
Park ChungGyu,
Oh Byung Hee,
Kim Suhnggwon,
Ahn Curie
Publication year - 2006
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2006.00311.x
Subject(s) - chemokine , monokine , immune system , cd8 , cxcr3 , infiltration (hvac) , immunology , biology , cxcl9 , cytokine , cxcl2 , cxcl10 , chemokine receptor , physics , thermodynamics
Background: The dynamic pattern of the cellular infiltration and mRNA expression of chemokines in rat‐to‐mouse skin xenografts were examined to gain an understanding of the possible role of chemokines in the stronger cellular immune responses to xenografts compared with the allo‐response. Methods: The mean survival time of the xenografts was approximately 2 days less than that of allografts (10.7 ± 0.9 days vs. 8.9 ± 0.7 days, P < 0.05). In comparison with the allografts, the xenografts were characterized by a very early infiltration of monocytes/macrophages (day 3) and a larger number of CD4 + and CD8 + cells, as well as neutrophil infiltration in the early phase (day 5), and larger number of CD8 + and CD11b + cells, as well as macrophage infiltration, in the later phase (day 7). Xenografts showed stronger interferon (IFN)‐inducible 10‐kDa protein (IP‐10) and monokine induced by IFN (MIG) mRNA expression levels, which appeared earlier than in the allografts. In the later phase, strong expression of regulated on activation, normal T cell expressed and secreted was observed. Cytokine mRNA expression in the xenografts could be summarized by higher expression of IFN‐ γ , interleukin (IL)1 β , IL6, and transforming growth factor ‐ β 1 mRNA than in the allografts. These results suggest that the early increased CXC‐chemokine expression, such as IP‐10 and MIG, which has been known to be mainly produced by macrophages, may play a critical role in the stronger cellular xenograft rejection compared with allograft rejection. Therefore, MIG antiserum or CXCR3 antiserum was administered to the rat skin‐engrafted mice every other day until rejection. Results: Compared with the control normal rabbit serum‐treated mice, either the MIG antiserum‐ or CXCR3 antiserum‐treated mice showed a delayed rejection of approximately 2 days (8.3 ± 0.5 days vs. 10.6 ± 0.5 days or 10.8 ± 1.9 days, respectively, P < 0.05). Conclusion: Overall, these results suggest that the more aggressive rejection of xenografts compared with allografts is due to the earlier expression of CXC‐chemokines, IP‐10 and MIG, and subsequent adjuvant effects of proinflammatory cytokines.