Effect of LFA-1 and ICAM-1 antibody treatment on murine corneal allograft survival

Y. He, J. Mellon, R. Apte, J. Y. Niederkorn

Research output: Contribution to journalArticle

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Abstract

Purpose. To examine the effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on orthotopic corneal graft survival in a mouse model. Methods. Anti-LFA-1 and anti-ICAM-1 antibodies were administered intraperitoneally before and shortly after orthotopic corneal transplantation. Grafts were observed by biomicroscopy, and survival times were determined. Cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses to donor alloantigens were assessed at selected times after grafting. Results. Administration of anti-LFA-1 antibody reduced the incidence of graft rejection from 90% in untreated donors to 47% in anti-LFA-1 treated mice. By contrast, treatment with anti-ICAM-1 antibody alone did not reduce the incidence of rejection, although it prolonged graft survival time. Both CTL and DTH responses to donor alloantigens were severely depressed in hosts treated with either anti-LFA-1 or anti-ICAM-1 antibody. However, neither anti-ICAM-1 nor anti-LFA-1 antibody treatment prevented the rejection of orthotopic corneal grafts in previously immunized mice. Conclusions. Anti- ICAM-1 antibody does not promote graft survival even though it impairs CTL and DTH responses to donor alloantigens. By contrast, anti-LFA-1 antibody can significantly reduce the incidence of orthotopic corneal graft rejection and prevent the induction of normal allospecific CTL and DTH responses. Although anti-LFA-1 antibody is effective if given prophylactically, it is ineffective at preventing corneal graft rejection in previously immunized hosts.

Original languageEnglish (US)
Pages (from-to)3218-3225
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume35
Issue number8
StatePublished - 1994

Fingerprint

Lymphocyte Function-Associated Antigen-1
Intercellular Adhesion Molecule-1
Allografts
Antibodies
Delayed Hypersensitivity
Cytotoxic T-Lymphocytes
Isoantigens
Graft Rejection
Graft Survival
Therapeutics
Incidence
Transplants
Corneal Transplantation

Keywords

  • antibody
  • intercellular cell adhesion molecule
  • keratoplasty
  • leukocyte function antigen
  • mouse

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Effect of LFA-1 and ICAM-1 antibody treatment on murine corneal allograft survival. / He, Y.; Mellon, J.; Apte, R.; Niederkorn, J. Y.

In: Investigative Ophthalmology and Visual Science, Vol. 35, No. 8, 1994, p. 3218-3225.

Research output: Contribution to journalArticle

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abstract = "Purpose. To examine the effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on orthotopic corneal graft survival in a mouse model. Methods. Anti-LFA-1 and anti-ICAM-1 antibodies were administered intraperitoneally before and shortly after orthotopic corneal transplantation. Grafts were observed by biomicroscopy, and survival times were determined. Cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses to donor alloantigens were assessed at selected times after grafting. Results. Administration of anti-LFA-1 antibody reduced the incidence of graft rejection from 90{\%} in untreated donors to 47{\%} in anti-LFA-1 treated mice. By contrast, treatment with anti-ICAM-1 antibody alone did not reduce the incidence of rejection, although it prolonged graft survival time. Both CTL and DTH responses to donor alloantigens were severely depressed in hosts treated with either anti-LFA-1 or anti-ICAM-1 antibody. However, neither anti-ICAM-1 nor anti-LFA-1 antibody treatment prevented the rejection of orthotopic corneal grafts in previously immunized mice. Conclusions. Anti- ICAM-1 antibody does not promote graft survival even though it impairs CTL and DTH responses to donor alloantigens. By contrast, anti-LFA-1 antibody can significantly reduce the incidence of orthotopic corneal graft rejection and prevent the induction of normal allospecific CTL and DTH responses. Although anti-LFA-1 antibody is effective if given prophylactically, it is ineffective at preventing corneal graft rejection in previously immunized hosts.",
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N2 - Purpose. To examine the effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on orthotopic corneal graft survival in a mouse model. Methods. Anti-LFA-1 and anti-ICAM-1 antibodies were administered intraperitoneally before and shortly after orthotopic corneal transplantation. Grafts were observed by biomicroscopy, and survival times were determined. Cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses to donor alloantigens were assessed at selected times after grafting. Results. Administration of anti-LFA-1 antibody reduced the incidence of graft rejection from 90% in untreated donors to 47% in anti-LFA-1 treated mice. By contrast, treatment with anti-ICAM-1 antibody alone did not reduce the incidence of rejection, although it prolonged graft survival time. Both CTL and DTH responses to donor alloantigens were severely depressed in hosts treated with either anti-LFA-1 or anti-ICAM-1 antibody. However, neither anti-ICAM-1 nor anti-LFA-1 antibody treatment prevented the rejection of orthotopic corneal grafts in previously immunized mice. Conclusions. Anti- ICAM-1 antibody does not promote graft survival even though it impairs CTL and DTH responses to donor alloantigens. By contrast, anti-LFA-1 antibody can significantly reduce the incidence of orthotopic corneal graft rejection and prevent the induction of normal allospecific CTL and DTH responses. Although anti-LFA-1 antibody is effective if given prophylactically, it is ineffective at preventing corneal graft rejection in previously immunized hosts.

AB - Purpose. To examine the effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on orthotopic corneal graft survival in a mouse model. Methods. Anti-LFA-1 and anti-ICAM-1 antibodies were administered intraperitoneally before and shortly after orthotopic corneal transplantation. Grafts were observed by biomicroscopy, and survival times were determined. Cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses to donor alloantigens were assessed at selected times after grafting. Results. Administration of anti-LFA-1 antibody reduced the incidence of graft rejection from 90% in untreated donors to 47% in anti-LFA-1 treated mice. By contrast, treatment with anti-ICAM-1 antibody alone did not reduce the incidence of rejection, although it prolonged graft survival time. Both CTL and DTH responses to donor alloantigens were severely depressed in hosts treated with either anti-LFA-1 or anti-ICAM-1 antibody. However, neither anti-ICAM-1 nor anti-LFA-1 antibody treatment prevented the rejection of orthotopic corneal grafts in previously immunized mice. Conclusions. Anti- ICAM-1 antibody does not promote graft survival even though it impairs CTL and DTH responses to donor alloantigens. By contrast, anti-LFA-1 antibody can significantly reduce the incidence of orthotopic corneal graft rejection and prevent the induction of normal allospecific CTL and DTH responses. Although anti-LFA-1 antibody is effective if given prophylactically, it is ineffective at preventing corneal graft rejection in previously immunized hosts.

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