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Role of tumor necrosis factor receptors TNFR-I (P55) and TNFR-II (P75) in corneal transplantation.
Transplantation. 1999 Oct 15; 68(7):944-9.T

Abstract

BACKGROUND

To determine the role of tumor necrosis factor-alpha (TNF-alpha) receptor (TNFR) function in corneal allograft immunology.

METHODS

Animals with gene-targeted deficiency in TNFR-I (p55-/-), TNFR-II (p75-/-), or combined TNFR-I/TNFR-II deficiency (p55-/-p75-/-) and their wild-type controls were used as recipients of fully-mismatched (BALB/c; n=88) or multiple minor alloantigen-mismatched (BALB.b; n=62) orthotopic corneal transplants to determine the effect of selective deficiency in one or both TNF-alpha receptors on corneal allograft survival. Grafted recipients were followed biomicroscopically for signs of rejection, and survival data were analyzed by the Kaplan-Meier method.

RESULTS

There was no discernible difference in survival of fully-mismatched BALB/c corneal grafts in p55-/- (n=12; P=0.76) or in double-knockout p55-/-p75-/- (n=13; P=0.41) as compared with wild-type C57BL/6.129 hosts. However, the survival of BALB/c allografts was lower in p75-/- (n=10; median survival 20 days) as compared with control C57BL/6 (n=30; median survival 30 days) hosts (P=0.02). In contrast, there was no discernible effect in survival of minor alloantigen-disparate BALB.b corneal grafts in p75-/- (n=13; P=0.95) or in combined p55-/-p75-/-(n=10; P=0.17) hosts as compared with C57BL/6 (n=9) and C57BL/6.129 (n=10) wild-type controls, respectively. However, there was a profound enhancement in the survival of BALB.b allografts in p55-/- recipients (n= 10; median survival 35 days) as compared to wild-type C57BL/6.129 (n=10; median survival 25 days) controls (P<0.01).

CONCLUSIONS

Our data suggest that the two TNF-alpha receptors largely play discrete roles in mediating rejection of murine corneal allografts. TNFR-I (p55) function seems to be integral to the rejection of minor-disparate grafts, and its selective suppression leads to enhancement of allograft survival. In contrast, TNFR-II (p75) function appears to be associated with enhanced survival of major histocompatibility complex-disparate allografts. The combined deletion of TNFR functionality in p55-/-p75-/- confers no net advantage or disadvantage to major histocompatibility complex or minor alloantigen-disparate grafts.

Authors+Show Affiliations

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10532532

Citation

Yamada, J, et al. "Role of Tumor Necrosis Factor Receptors TNFR-I (P55) and TNFR-II (P75) in Corneal Transplantation." Transplantation, vol. 68, no. 7, 1999, pp. 944-9.
Yamada J, Streilein JW, Dana MR. Role of tumor necrosis factor receptors TNFR-I (P55) and TNFR-II (P75) in corneal transplantation. Transplantation. 1999;68(7):944-9.
Yamada, J., Streilein, J. W., & Dana, M. R. (1999). Role of tumor necrosis factor receptors TNFR-I (P55) and TNFR-II (P75) in corneal transplantation. Transplantation, 68(7), 944-9.
Yamada J, Streilein JW, Dana MR. Role of Tumor Necrosis Factor Receptors TNFR-I (P55) and TNFR-II (P75) in Corneal Transplantation. Transplantation. 1999 Oct 15;68(7):944-9. PubMed PMID: 10532532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of tumor necrosis factor receptors TNFR-I (P55) and TNFR-II (P75) in corneal transplantation. AU - Yamada,J, AU - Streilein,J W, AU - Dana,M R, PY - 1999/10/26/pubmed PY - 1999/10/26/medline PY - 1999/10/26/entrez SP - 944 EP - 9 JF - Transplantation JO - Transplantation VL - 68 IS - 7 N2 - BACKGROUND: To determine the role of tumor necrosis factor-alpha (TNF-alpha) receptor (TNFR) function in corneal allograft immunology. METHODS: Animals with gene-targeted deficiency in TNFR-I (p55-/-), TNFR-II (p75-/-), or combined TNFR-I/TNFR-II deficiency (p55-/-p75-/-) and their wild-type controls were used as recipients of fully-mismatched (BALB/c; n=88) or multiple minor alloantigen-mismatched (BALB.b; n=62) orthotopic corneal transplants to determine the effect of selective deficiency in one or both TNF-alpha receptors on corneal allograft survival. Grafted recipients were followed biomicroscopically for signs of rejection, and survival data were analyzed by the Kaplan-Meier method. RESULTS: There was no discernible difference in survival of fully-mismatched BALB/c corneal grafts in p55-/- (n=12; P=0.76) or in double-knockout p55-/-p75-/- (n=13; P=0.41) as compared with wild-type C57BL/6.129 hosts. However, the survival of BALB/c allografts was lower in p75-/- (n=10; median survival 20 days) as compared with control C57BL/6 (n=30; median survival 30 days) hosts (P=0.02). In contrast, there was no discernible effect in survival of minor alloantigen-disparate BALB.b corneal grafts in p75-/- (n=13; P=0.95) or in combined p55-/-p75-/-(n=10; P=0.17) hosts as compared with C57BL/6 (n=9) and C57BL/6.129 (n=10) wild-type controls, respectively. However, there was a profound enhancement in the survival of BALB.b allografts in p55-/- recipients (n= 10; median survival 35 days) as compared to wild-type C57BL/6.129 (n=10; median survival 25 days) controls (P<0.01). CONCLUSIONS: Our data suggest that the two TNF-alpha receptors largely play discrete roles in mediating rejection of murine corneal allografts. TNFR-I (p55) function seems to be integral to the rejection of minor-disparate grafts, and its selective suppression leads to enhancement of allograft survival. In contrast, TNFR-II (p75) function appears to be associated with enhanced survival of major histocompatibility complex-disparate allografts. The combined deletion of TNFR functionality in p55-/-p75-/- confers no net advantage or disadvantage to major histocompatibility complex or minor alloantigen-disparate grafts. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/10532532/Role_of_tumor_necrosis_factor_receptors_TNFR_I__P55__and_TNFR_II__P75__in_corneal_transplantation_ L2 - https://doi.org/10.1097/00007890-199910150-00008 DB - PRIME DP - Unbound Medicine ER -