The influence of cervical and thoracic lymphadenectomy on corneal allograft rejection in inbred rats

Aim To investigate the site of alloantigen presentation in the rat following orthotopic corneal transplantation. Methods Adult inbred Fischer 344 rats received penetrating corneal allografts from inbred Wistar Furth donors (n=17), without lymphadenectomy. A second group (n=8) underwent bilateral removal of superficial cervical and facial lymph nodes 7 days before transplantation. A third group (n=9) underwent bilateral removal of superficial cervical, facial, internal jugular and posterior cervical nodes. Graft survival was assessed by corneal clarity and rejection was confirmed histologically. Results All allografts underwent rejection. The median time to rejection for unmodified allografts was day 15, compared with day 14.5 for minimally lymphadenectomised recipients and day 18 for more extensively lymphadenectomised recipients (p>0.05, all comparisons). The median day to rejection for the combined group of lymphadenectomised rats was day 17 (p>0.05 compared with unmodified grafts). The rejection process was similar in all recipients. Conclusions Removal of multiple lymph nodes in the neck and thorax did not significantly influence the incidence, tempo or nature of the corneal allograft response. Sensitisation and clonal expansion of corneal alloantigen-reactive cells cannot occur only in superficial cervical, facial, internal jugular and posterior cervical lymph nodes in the rat.

[1]  E. Knop,et al.  Regulation of the inflammatory component in chronic dry eye disease by the eye-associated lymphoid tissue (EALT). , 2010, Developments in ophthalmology.

[2]  N. Gupta,et al.  Identification of lymphatics in the ciliary body of the human eye: a novel "uveolymphatic" outflow pathway. , 2009, Experimental eye research.

[3]  M. Ross,et al.  Sentinel lymph node biopsy for ocular adnexal melanoma: experience in 30 patients. , 2009, Ophthalmology.

[4]  Huang Yanhua,et al.  Ipsilateral lymphadenectomy to inhibit corneal allograft rejection in rats , 2008, Journal of Huazhong University of Science and Technology [Medical Sciences].

[5]  P. McMenamin,et al.  Characterisation of rat corneal cells that take up soluble antigen: an in vivo and in vitro study. , 2006, Experimental eye research.

[6]  W. Van den Broeck,et al.  Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice. , 2006, Journal of immunological methods.

[7]  P. Rigby,et al.  Antigen from the anterior chamber of the eye travels in a soluble form to secondary lymphoid organs via lymphatic and vascular routes. , 2006, Investigative ophthalmology & visual science.

[8]  D. Coster,et al.  The impact of corneal allograft rejection on the long-term outcome of corneal transplantation. , 2005, American journal of ophthalmology.

[9]  J. Scheerlinck,et al.  Prolongation of Sheep Corneal Allograft Survival by Transfer of the Gene Encoding Ovine IL-12-p40 but Not IL-4 to Donor Corneal Endothelium1 , 2005, The Journal of Immunology.

[10]  M. Thiel,et al.  Local gene transfer to modulate rat corneal allograft rejection. , 2005, Investigative ophthalmology & visual science.

[11]  J. Forrester,et al.  Lymph node removal enhances corneal graft survival in mice at high risk of rejection , 2004, BMC ophthalmology.

[12]  F. Hoffmann,et al.  Ipsilateral submandibular lymphadenectomy does not prolong orthotopic corneal graft survival in mice , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[13]  A. Dick,et al.  Development of organised conjunctival leucocyte aggregates after corneal transplantation in rats , 2003, The British journal of ophthalmology.

[14]  M. Dana,et al.  Draining Lymph Nodes Play an Essential Role in Alloimmunity Generated in Response to High-Risk Corneal Transplantation , 2002, Cornea.

[15]  J. Forrester,et al.  THE IMMUNE RESPONSE TO CORNEAL ALLOGRAFT REQUIRES A SITE-SPECIFIC DRAINING LYMPH NODE1 , 2002, Transplantation.

[16]  R. Dana,et al.  Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts , 2002, The Journal of experimental medicine.

[17]  F. Hoffmann,et al.  Contribution of lymphatic drainage system in corneal allograft rejection in mice , 2001, Graefe's Archive for Clinical and Experimental Ophthalmology.

[18]  S. Klebe,et al.  PROLONGATION OF SHEEP CORNEAL ALLOGRAFT SURVIVAL BY EX VIVO TRANSFER OF THE GENE ENCODING INTERLEUKIN-101 , 2001, Transplantation.

[19]  R. Dana,et al.  The critical role of lymph nodes in corneal alloimmunization and graft rejection. , 2001, Investigative ophthalmology & visual science.

[20]  J. Woodward,et al.  In Vivo Behavior of Peptide-Specific T Cells During Mucosal Tolerance Induction: Antigen Introduced Through the Mucosa of the Conjunctiva Elicits Prolonged Antigen-Specific T Cell Priming Followed by Anergy1 , 2000, The Journal of Immunology.

[21]  E. Knop,et al.  Conjunctiva-associated lymphoid tissue in the human eye. , 2000, Investigative ophthalmology & visual science.

[22]  D. Coster,et al.  Penetrating corneal transplantation in the inbred rat: a new model. , 1985, Investigative ophthalmology & visual science.

[23]  W. M. Bourne,et al.  The effect of splenectomy on corneal graft rejection. , 1976, Investigative ophthalmology.

[24]  H. Kaplan,et al.  Do immunologically privileged sites require a functioning spleen? , 1974, Nature.

[25]  N L Tilney,et al.  Patterns of lymphatic drainage in the adult laboratory rat. , 1971, Journal of anatomy.

[26]  A. S. Wiener,et al.  Transplantation , 1963 .