Immunobiology of Corneal Transplants

Immune Privilege and Retinal Transplantation

Effects of Ultraviolet-B on Contact Hypersensitivity

Current Research Projects:

Immunobiology of Corneal Transplants

The great majority of primary keratoplasties in human beings succeed, but an intolerably high proportion of allogeneic corneal grafts placed in “high-risk” eyes fail.

Since immune rejection is regarded as the major cause of graft failure, the long-term goals of this project are to understand the cellular and molecular immune processes that dictate (a) why primary orthotopic corneal allografts are so well tolerated, and (b) why grafts in “high-risk” eyes fare so poorly. Our laboratory has studied the fate of allogeneic orthotopic corneal transplants in mice and determined that (a) the majority of highly incompatible grafts are accepted and survive indefinitely, (b) so-called minor histocompatibilities are the more potent immunogens expressed by the cornea, (c) mice with long-accepted cornea allografts display donor-specific Anterior Chamber Associated Immune Deviation (ACAID), and (d) allogeneic corneas placed at heterotopic graft sites display inherent immune privilege due to expression of CD95 ligand. Current research is aimed at (a) understanding the pathogenesis of acute and delayed rejection of corneal xenotransplants, (b) describing the unique pathway of expression of class II MHC molecules on corneal endothelial cells, and (c) identifying the extent to which self-peptides displayed on recipient MHC class I and II MHC molecules promote acceptance and rejection of allogeneic cornea transplants.

Expression of MHC class II molecules on interferon-gamma + tumor necrosis-alpha-treated murine corneal endothelial cells, as determined by (G) flow cytometry and (H) confocal microscopy.

Grant Support
NIH EY10765, “Immunobiology of Corneal Transplants”

Current Postdoctoral Fellows
Leonardo Borges, M.D.
Claus Cursiefen, M.D.
Charles Kim, M.D.

Current Collaborators
Bruce R. Ksander, Ph.D., M. Reza Dana, M.D., M.P.H., Jacqueline M. Doherty, Ph.D.Papers Published/In Press since January 1, 2002.

CORNEAL ALLOGRAFTS AND IMMUNE PRIVILEGE

Hori, Junko, Joyce, N., and Streilein, J. W. Corneal allografts placed beneath the kidney capsule display inherent immune privilege. Invest. Ophthal. Vis. Sci. 41: 443 – 452, 2000.

Hori, J., Joyce, N., and Streilein, J.W. Where immune privilege and immunogenicity reside among different layers of the mouse cornea. Invest. Ophthal. Vis. Sci. 41: 3032 – 3042, 2000.

Hori, J., and Streilein, J.W. Role of recipient epithelium in promoting survival of orthotopic corneal allografts in mice. Invest. Ophthal. Vis. Sci. 42: 720 – 726, 2001.

Fate of guinea pig cornea grafts placed orthotopically in eyes of SCID mice reconstituted with unfractionated spleen cells or CD4-depleted spleen cells of normal BALB/c mice.

CORNEAL ALLOGRAFT REJECTION MECHANISMS

Sano, Yoichiro, Ksander, B.R., and Streilein, J.W. Langerhans cells, orthotopic corneal allografts, and direct and indirect pathways of T cell allorecognition. Invest. Ophthal, Vis. Sci. 41: 1422 – 1431, 2000.

Sano, Y., Ksander, B.R., and Streilein, J.W. Analysis of primed donor-specific T cells in recipient mice bearing orthotopic corneal allografts. Transplantation 70: 1302 – 1310, 2000.

Streilein, J.W. What do T lymphocytes “see” when penetrating keratoplasty fails? Cornea 19: S146
– S154, 2000.

Yamada, J., Ksander, B.R., and Streilein, J.W. Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice. Invest. Ophthal. Vis. Sci. 42: 386 – 392, 2001.

Hori, J., and Streilein, J.W. Dynamics of donor cell persistence and recipient cell replacement in orthotopic corneal allografts in mice. Invest. Ophthal. Vis. Sci. 42: 1820 – 1828, 2001.

CORNEAL ALLOGRAFTS AND ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION

Sonoda, A., Sonoda, Y., Muramatu, R., Streilein, J.W., and Usui, M. ACAID induced by allogeneic corneal tissue promotes subsequent survival of orthotopic corneal grafts. Invest. Ophthal. Vis. Sci. 41:790 – 798, 2000.

Yamada, J., Zhu, S.N., Streilein, J.W. and Dana, M.R. Interleukin-1 receptor antagonist therapy and induction of anterior chamber associated immune deviation (ACAID)-type tolerance after corneal transplantation. Invest. Ophthal. Vis. Sci. 41: 4203 – 4208, 2000.

FATE OF CORNEAL XENOGRAFTS IN MICE

Tanaka, K., Yamada, J., Joyce, N. and Streilein, J.W. Immunobiology of xenogeneic cornea grafts in mouse eyes. I. Fate of xenogeneic cornea tissue grafts implanted in anterior chamber of mouse eyes. Transplantation 69: 610-616, 2000.

Tanaka, K., and Streilein, J.W. Immunobiology of xenogeneic cornea grafts in mouse eyes. II. Immunogenicity of xenogeneic cornea tissue grafts implanted in anterior chamber of mouse eyes. Transplantation 69: 616-623, 2000.

Fate of guinea pig cornea grafts placed orthotopically in eyes of SCID mice reconstituted (or not) with CD8+ T cells prepared from normal BALB/c mice.

Tanaka, K., Yamada, J., and Streilein, J.W. Xenoreactive CD4+ T cells, but not CD8+ T cells or antibodies, are responsible for acute rejection of orthotopic guinea pig corneas in mice. Invest. Ophthal. Vis. Sci. 41: 1827 – 1832, 2000.
Tanaka, K., Sonoda, K-H, and Streilein, J.W. Acute rejection of orthotopic corneal xenografts in mice depends on CD4+ T cells and self antigen-presenting cells in mice. Invest. Ophthal. Vis. Sci. 42: 2878 – 2884, 2001.