Characterization of cytokine profiles in corneal allograft with anti-adhesion therapy.
BACKGROUND
The cytokine profiles of specific immunosuppression after anti-adhesion molecule therapy are unknown in a mouse corneal transplantation model.


METHODS
Orthotopic mouse corneal transplantation was performed using BALB/c (H-2d) mice as recipients and C3H/He (H-2k) mice as donors. Anti-mouse very late antigen-4 and anti-mouse lymphocyte function-associated antigen-1 monoclonal antibodies (each at a dose of 0.25/mg/day) were administered i.p. until day 7. A second corneal transplantation was performed 5 weeks after the first grafting. Delayed hypersensitivity was tested after the second grafting. Corneal cytokine expression was examined immunohistochemically. The cytokine gene transcription level was assessed in the corneas and splenocytes.


RESULTS
All allografts with anti-adhesion molecule therapy survived for 5 weeks. Two weeks after the second grafts in the fellow eye (7 weeks after the first grafts), 50% of the mice with successful grafts bilaterally had low delayed hypersensitivity responses. Low helper T 1 (interferon-gamma and interleukin-2) cytokine gene and protein expression in corneas was observed in monoclonal antibody-treated mice 3 weeks after the first grafting. The mice with successful second grafts showed low corneal T helper 1 cytokine gene and protein expression. High interleukin-4 gene transcription levels in corneas and splenocytes was obtained in both groups in which the grafts were accepted and rejected after the second grafts.


CONCLUSIONS
The cytokine profile to differentiate alloantigen-specific acceptance with anti-adhesion therapy to lymphocyte function-associated antigen-1 and very late antigen-4 molecules from rejection after the second grafting is local and systemic low T helper 1 cytokine in corneal transplantation. High interleukin-4 cytokine expression in corneas and splenocytes is not associated with achievement of tolerance induction.
Yamagami
S
S
Department of Ophthalmology, Jichi Medical School, Kawachi, Tochigi, Japan.
Isobe
M
M
Tsuru
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D016039:Corneal Transplantation / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013154:Spleen / Q000473:pathology / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma