Termination of immune privilege in the anterior chamber of the eye when tumor-infiltrating lymphocytes acquire cytolytic function.
Minor H incompatible P815 tumor cells form progressively growing intraocular tumors when injected into the anterior chamber of eyes of BALB/c mice (an immunologically privileged site), but these tumor cells are promptly rejected when injected into the subconjunctival space. In both circumstances, the tumor inoculation site acquires significant numbers of DBA/2-specific precursor cytotoxic T cells (pTc) but only at the subconjunctival site do fully functional cytotoxic T cells (Tc) emerge, and their emergence coincides temporally with rejection of the tumor graft. In the present study, we wished to determine whether pTc can differentiate into Tc within the anterior chamber of the eye and whether the failure of BALB/c mice to reject intraocular P815 tumors is related to this putative block in pTc differentiation. It was previously shown that P815 tumor cells injected into the eyes of MHC-incompatible C57BL/6 mice are able to grow transiently within the anterior chamber and that they are eventually rejected. We have examined the local cytotoxic T cell responses during and after the transient phase of immune privilege that is extended to MHC-incompatible tumor grafts in eyes of C57BL/6 mice. Our results indicate that termination of immune privilege (rejection of the tumor implant) coincides with the detection of fully functional Tc within the tumor-containing eye. Circumstantial evidence suggests that these tumors are infiltrated with DBA/2-specific pTc during the phase of progressive tumor growth and that it is these infiltrating cells that differentiate in oculi into the Tc that effect graft rejection. These findings support the hypotheses that immune privilege in the anterior chamber of the eye is an actively maintained process that suppresses terminal differentiation of pTc and that privilege is abolished if conversion of pTc to Tc is accomplished.
Ksander
B R
BR
Department of Microbiology and Immunology, University of Miami Medical School, Florida 33136.
Mammolenti
M M
MM
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005134:Eye Neoplasms / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*