title: The critical role of lymph nodes in corneal alloimmunization and graft rejection.
abstract: OBJECTIVE
  To elucidate the role of draining cervical lymph nodes (CLNs) in corneal alloimmunity.
  
  
  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 transplantation.
authors.affiliation: Laboratory of Immunology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamagami
authors.forename: M R
authors.initials: MR
authors.lastname: Dana
mesh_terms: D000818:Animals; D003315:Cornea / Q000276:immunology*; D016039:Corneal Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007109:Immunity; D007114:Immunization; D008198:Lymph Nodes / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009333:Neck; D013154:Spleen / Q000276:immunology; D013156:Splenectomy; D014184:Transplantation, Homologous