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Tanja P. A. M. Slegers, Paulo F. Torres, Lidy Broersma, Nico van Rooijen, Gabriel van Rij, Ruth van der Gaag; Effect of Macrophage Depletion on Immune Effector Mechanisms during Corneal Allograft Rejection in Rats. Invest. Ophthalmol. Vis. Sci. 2000;41(8):2239-2247.
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purpose. In rats, corneal allograft rejection is delayed for at least 100 days
by clodronate liposomes. These liposomes selectively deplete
macrophages. To investigate the immunologic basis for absence of graft
rejection in treated rats, the effect of these liposomes on the
generation of cytotoxic T lymphocytes (CTLs) and antibody production
after orthotopic corneal allotransplantation was determined.
methods. Transplantations of corneal buttons from PVG rats were performed in AO
rats. After surgery, one group received clodronate liposomes
subconjunctivally at five time points, and the other group remained
untreated. On postoperative day (POD) 3, 7, 12, or 17, rats were
killed, the presence of CTLs was investigated at three different
anatomic locations, and antibodies against donor antigens were tested.
results. No significant differences were found between the groups tested 3 and 7
days after surgery. But on POD 12 (the time of onset of rejection in
the untreated group) and on POD 17, the CTL activities detected in the
submandibular lymph nodes (P ≤ 0.008) and the spleen
(P ≤ 0.009) were significantly less in the treated
groups compared with the untreated groups. In the untreated groups
complement-independent antibodies were present only on POD 17, whereas
no antibodies were found in the treated rats.
conclusions. Local treatment with clodronate liposomes was shown to downregulate
local and systemic CTL responses and to prevent the generation of
antibodies. Local depletion of macrophages in the initiation phase of
the immune response appears to lead to a less vigorous attack on the
grafted tissue and therefore to promote graft
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