Intraocular tumor antigen drains specifically to submandibular lymph nodes, resulting in an abortive cytotoxic T cell reaction.
Ocular immune privilege is considered essential in the protection against sight-threatening immune responses, as illustrated by the ability of the ocular environment to permit the growth of tumors that are rejected when implanted at other sites. Although several studies indicate that soluble Ag can drain directly into the spleen when injected into the anterior chamber, the primary site of intraocular tumor Ag presentation to tumor-specific CTLs has not been studied. To gain a better understanding of the mechanism involved in ocular immune privilege, we examined to which lymphoid organs anterior chamber tumor Ags primarily drain. Our data show that intraocular tumor Ag drains exclusively to the submandibular lymph nodes, resulting in activation of tumor-specific CTLs, whereas no Ag drainage was found in spleen. However, these tumor-specific CTLs do not distribute systemically and, as a consequence, intraocular tumor growth is unhampered. A similar lack of CTL efficacy has been observed in mice bearing s.c. tumors, which is converted to a systemic tumoricidal CTL response by administration of agonistic anti-CD40 mAb. In contrast, systemic anti-CD40 treatment of eye tumor-bearing mice did not result in mobilizing tumor-specific CTLs or tumor eradication. Together, these results show that intraocular tumor Ag drains to regional lymph nodes for activation of tumor-specific CTLs. However, the induced tumor-specific immunity is insufficient for tumor clearance, even combined with otherwise highly effective immune intervention protocols.
Boonman
Zita F H M
ZF
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
van Mierlo
Geertje J D
GJ
Fransen
Marieke F
MF
Franken
Kees L M C
KL
Offringa
Rienk
R
Melief
Cornelis J M
CJ
Jager
Martine J
MJ
Toes
René E M
RE
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000818:Animals; D000867:Anterior Chamber / Q000276:immunology / Q000473:pathology / Q000821:virology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D013363:Submandibular Gland / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D017500:Adenovirus E1A Proteins; D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte