December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
In CD4+ T Cell Deficient Mice, Th1-like CD8+ T Cells Effect Delayed Rejection of Orthotopic Guinea Pig Cornea Xenografts Via IFN- Rather Than Cytotoxicity
Author Affiliations & Notes
  • R Higuchi
    Ophthalmology Schepens Eye Research Institute Boston MA
  • JW Streilein
    Ophthalmology Schepens Eye Research Institute Boston MA
  • Footnotes
    Commercial Relationships   R. Higuchi, None; J.W. Streilein, None. Grant Identification: EY10765
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2273. doi:
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      R Higuchi, JW Streilein; In CD4+ T Cell Deficient Mice, Th1-like CD8+ T Cells Effect Delayed Rejection of Orthotopic Guinea Pig Cornea Xenografts Via IFN- Rather Than Cytotoxicity . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2273.

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Abstract

Abstract: : Purpose: To determine the immunopathogenesis of delayed rejection of orthotopic corneal xenografts in mice deficient in CD4+ T cells that mediate acute rejection. Methods: CB.17 SCID mice received orthotopic guinea pig cornea grafts. Some mice received intraperitoneal injections of hyperimmune mouse anti-guinea pig antiserum at 30 and 33 days post-grafting. Other SCID mice were reconstituted with purified CD8+ T cells from naive BALB/c donors immediately prior to grafting. Naive BALB/c mice grafted orthotopically with guinea pig corneas served as positive controls. Graft survival was assessed by clinical examination. Draining cervical lymph node cells were collected at 28 days (coincident with graft rejection) and assayed for (a) cytotoxicity directed at guinea pig target cells, (b) capacity to proliferate and secrete IFN-γ when stimulated in vitro with guinea pig spleen cell stimulators. Results: CD8+ T cell-reconstituted SCID mice rejected guinea pig corneas within 28 days, whereas SCID recipients of hyperimmune sera failed to reject their grafts. Draining lymph node cells removed on day 28 from CD8+ T cell reconstituted SCID mice, as well as from positive control mice, failed to lyse guinea pig target cells in vitro, but when stimulated with guinea pig spleen cells in vitro, the responding T cells proliferated and secreted IFN-γ. Anti-CD8+ antibodies added to cultures containing lymph node cells from CD8+ T cell-reconstituted SCID mice abolished proliferation and IFNγ production. Conclusion: In the absence of CD4+ T cells, mice utilize CD8+ T cells, but not antibodies, to reject guinea pig cornea xenografts. These helper cell-independent effector CD8+ T cells resemble Th1 cells and destroy the graft through release of IFN-γ, rather than via cytotoxicity.

Keywords: 370 cornea: basic science • 607 transplantation • 316 animal model 
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