Role of interferon‐γ and cytotoxic T lymphocytes in intraocular tumor rejection

[摘要] Theeyeisnormallyanimmunosuppressiveenvironment.Thisconditionisbetterknownasimmuneprivilegeandprotectstheeyefromimmune‐mediatedinflammationoftissuesthatcannotregenerate.However,immuneprivilegecreatesadilemmafortheeyewhenintraocularneoplasmsarise.Insomecases,immuneprivilegeissuspended,resultingintheimmunerejectionofintraoculartumors.Thisstudyemployedamousemodelinwhichinterferon‐γ–dependentintraoculartumorrejectionoccurs.Wetestedthehypothesisthatthisrejectionrequiresinterferon‐γforthegenerationandfunctionalcapacityofcytotoxicTlymphocyte–mediatedrejectionofintraoculartumors.Tumorsgrewprogressivelyintheeyesofinterferon‐γknockoutmice,eventhoughthemicegeneratedtumor‐specificcytotoxicTlymphocyteresponsesintheperiphery.However,interferon‐γknockoutmicerejectedtumorsthatwereintroducedintoextraocularsites.Subcutaneoustumorimmunizationbeforeintraocularchallengeledtotumorrejectionandpreservationoftheeyeinwild‐typemice.Bycontrast,tumorsgrewprogressivelyintheeyesofinterferon‐γknockoutmicedespitetheirabilitytogenerateperipheraltumor‐specificcytotoxicTlymphocytesaswellasthecapacityofCD8+TcellstoentertheeyeasshownbythepresenceofCD8andperforinmessageandCD3+CD8+leukocyteswithinthetumor‐bearingeye.WefoundthatcytotoxicTlymphocytesgeneratedinwild‐typemiceandadoptivelytransferredintointerferon‐γknockoutmicemediatedtherejectionofintraoculartumorsininterferon‐γknockouthosts.Theresultsindicatethatinterferon‐γiscriticalfortheinitialpriminganddifferentiationofcytotoxicTlymphocytesresidingintheperipherytoproducethemosteffectantitumorfunctionwithintheeye...

[学科分类] 生理学

[关键词] eye;immune privilege;necrotic inflammation;CTL;IFN‐γ