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Satoru Yamagami, M. Reza Dana; The Critical Role of Lymph Nodes in Corneal Alloimmunization and Graft Rejection. Invest. Ophthalmol. Vis. Sci. 2001;42(6):1293-1298.
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purpose. To elucidate the role of draining cervical lymph nodes (CLNs) in
methods. Fully mismatched orthotopic corneal transplantation was performed in
BALB/c hosts that had their CLNs excised before transplantation
(CLN−). Normal hosts (CLN+), splenectomized
mice (Sp−), and those without either CLNs or spleen
(CLN−/Sp−) served as comparison groups. To
determine the contribution of CLNs to alloimmunity more directly,
CLN− mice were reconstituted by grafting LNs from other
BALB/c mice to their cervical lymphatic chains, thus deriving
CLN−/+ mice. Tetramethyl rhodamine isothiocyanate’s
(TRITC) flow to draining CLNs was used as a measure of afferent lymph
flow. Graft survival and allospecific delayed-type hypersensitivity
(DTH) were used as measures of alloreactivity.
results. Fifty percent of normal control and 12% of Sp− hosts
accepted the allografts. In contrast, 100% of CLN− and
88% of CLN−/Sp− hosts accepted allografts
indefinitely (P < 0.01). Additionally, all
CLN− hosts failed to demonstrate allospecific DTH
(P < 0.001). CLN−/+ mice
reconstituted with LN from naïve animals showed graft survival
rates and DTH responses that were indistinguishable from those of
naïve CLN+ mice. Of particular interest, however,
is that mice reconstituted with CLNs from hosts with rejected corneal
grafts had swift rejection of subsequent corneal grafts and exhibited
strong donor-specific DTH. In contrast, mice reconstituted with CLNs
from hosts with accepted corneal grafts showed rejection of subsequent
corneal grafts in a manner that was indistinguishable from rejection in
naïve CLN+ hosts.
conclusions. Draining CLNs play a critical role in allosensitization and rejection.
In contrast to the spleen, draining CLNs do not appear to play a
critical role in tolerance induction in corneal
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