Effect of local macrophage depletion on cellular immunity and tolerance evoked by corneal allografts.
Corneal graft rejection can be prevented by local macrophage depletion, via subconjunctival injections with clodronate liposomes. To unravel the underlying immunological mechanism responsible for prolonged graft survival in this circumstance, the effect of this regimen on induction of donor-specific delayed type hypersensitivity (DTH) and anterior chamber associated immune deviation (ACAID) was determined. The study showed that although subconjunctival clodronate liposome-treatment failed to alter systemically induced DTH and ACAID, both types of immune response were absent in clodronate liposome-treated rats after corneal transplantation. Thus, elimination of macrophages from the corneal transplant site renders corneal allografts immunologically "invisible" to the recipient.


OBJECTIVE
To determine whether local macrophage depletion, via administration of clodronate liposomes, alters delayed type hypersensitivity (DTH) responses and induction of anterior chamber associated immune deviation (ACAID) after corneal allotransplantation.


METHODS
Clodronate liposome-treated and untreated rats received orthotopic corneal allografts and were tested for DTH responses and induction of ACAID towards donor antigens. Also in subconjunctivally treated and untreated rats, DTH responses were measured after subcutaneous immunization or induction of ACAID with allogeneic spleen cells.


RESULTS
Subconjunctival injected clodronate liposomes prevented grafted rats from developing donor-specific DTH as well as ACAID. By contrast, subconjunctivally injected clodronate liposomes had no effect on donor-specific DTH responses after systemic immunization or on the induction of ACAID with allogeneic cells.


CONCLUSIONS
Depletion of macrophages at the time of corneal allografting seems to render the grafts immunologically invisible to the recipients. This could explain why these grafts survive "indefinitely" without any other form of therapy.
Slegers
Tanja P A M
TP
Department of Ophthalmology, University Hospital Groningen, The Netherlands. t.slegers@ohk.azg.nl
van der Gaag
Ruth
R
van Rooijen
Nico
N
van Rij
Gabriel
G
Streilein
J Wayne
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D004002:Clodronic Acid / Q000008:administration & dosage; D016039:Corneal Transplantation / Q000276:immunology*; D004337:Drug Carriers; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D007519:Isoantigens; D008081:Liposomes; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D004337:Drug Carriers; D007519:Isoantigens; D008081:Liposomes; D004002:Clodronic Acid