[Immunomodulation after keratoplasty by CTL4-Ig and anti-CD154 antibodies].
BACKGROUND
The immunoreaction after corneal transplantation is caused by the T cell receptor interacting with the major histocompatibility complex (MHC) receptor of the antigen-presenting cell. The signal is amplified by the CD4 receptor and the costimulatory signal interactions of CD28-B7 and CD40-CD154. We investigated the influence of costimulatory signal blocking on corneal transplant survival in mice.


METHODS
Seven groups of 6 BALB/c mice received an orthotopic corneal transplant from C3H mice differing in minor and major MHC and were postoperatively treated as follows: (1) 80 micrograms of CTLA4 fusion protein intraperitoneally (i.p.) for 6 days; (2) 50 microliters of PBS i.p. for 6 days; (3) 1 mg of Solu-Decortin H i.p. for 5 days + dexamethasone AT 0.1% for 35 days; (4) therapy (3) + 50 micrograms of CTLA4 fusion protein i.p. for 6 days; (5) CTLA4-Ig as in (1) + 15 micrograms of anti-CD154 subconjunctivally (s.c.) on days 0, 2, 4, 6, and 8; (6) CTLA4-Ig as in (1) + 25 micrograms of anti-CD154 s.c. for 9 days; and (7) 25 microliters of PBS s.c. for 9 days.


RESULTS
All animals had an immunoreaction on the following days: (1) day 18 +/- 3.1; (2) day 13.6 +/- 1.6; (3) day 48 +/- 6.6; (4) day 65 +/- 41; (5) day 23.5 +/- 8.5; (6) day 16.2 +/- 3.6; (7) day 13.8 +/- 2.7.


CONCLUSIONS
The significant prolongation of transplant survival achieved by corticosteroids alone (P < 0.001) is again significantly increased by combining them with CTLA4-Ig (P < 0.001). Specific immunotherapy combined with nonspecific steroid therapy may also improve clinical corneal transplantation results. Compared to the two control groups, CTLA4-Ig and anti-CD154 only influenced transplant survival at a low dosage (P < 0.001).
Zhang
E P
EP
Universitätsklinikum Benjamin Franklin, Augenklinik, Berlin.
Bulfone-Paus
S
S
Hoffmann
F
F
D000069594:Abatacept; D000276:Adjuvants, Immunologic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D060908:CTLA-4 Antigen; D016039:Corneal Transplantation; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D023201:CD40 Ligand; D003900:Desoxycorticosterone; D000069594:Abatacept; D003907:Dexamethasone
Immunmodulation nach Keratoplastik durch CTLA4-Ig und anti-CD154-Antikörper.