Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes

Ding Ma, Hassan Alizadeh, Sarah A Comerford, Mary Jane Gething, Joseph F. Sambrook, Rajiv Anand, Jerry Y Niederkorn

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice. Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice and the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. The role of CD4+ and CD8+ T cells in intraocular tumor rejection was evaluated by depleting the respective cell populations in FVB/N hosts prior to intraocular tumor challenge. The results showed that intraocular tumors undergoing rejection in immunocompetent syngeneic hosts became infiltrated with T cells, with the CD8+ subset predominating at the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL. TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted of CD4+ T cells were unable to reject their intraocular tumors. In vivo depletion of CD8+ T cells delayed, but did not prevent tumor rejection. Adoptively transferred TIL mediated swift rejection of intraocular tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specific CTL activity that was demonstrable in vitro. The results strongly suggest, but do not prove, that TIL mediate rejection of intraocular tumors from transgenic mice by direct cytolysis. Although CD4+ T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8+ CTL.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalCurrent Eye Research
Volume13
Issue number5
DOIs
StatePublished - 1994

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Tumor-Infiltrating Lymphocytes
Transgenic Mice
Neoplasms
T-Lymphocytes
Nude Mice

Keywords

  • Choroid
  • Cytotoxic T lymphocyte
  • Intraocular tumor
  • Rejection
  • Transgenic mouse

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes. / Ma, Ding; Alizadeh, Hassan; Comerford, Sarah A; Gething, Mary Jane; Sambrook, Joseph F.; Anand, Rajiv; Niederkorn, Jerry Y.

In: Current Eye Research, Vol. 13, No. 5, 1994, p. 361-369.

Research output: Contribution to journalArticle

Ma, Ding ; Alizadeh, Hassan ; Comerford, Sarah A ; Gething, Mary Jane ; Sambrook, Joseph F. ; Anand, Rajiv ; Niederkorn, Jerry Y. / Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes. In: Current Eye Research. 1994 ; Vol. 13, No. 5. pp. 361-369.
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AB - The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice. Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice and the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. The role of CD4+ and CD8+ T cells in intraocular tumor rejection was evaluated by depleting the respective cell populations in FVB/N hosts prior to intraocular tumor challenge. The results showed that intraocular tumors undergoing rejection in immunocompetent syngeneic hosts became infiltrated with T cells, with the CD8+ subset predominating at the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL. TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted of CD4+ T cells were unable to reject their intraocular tumors. In vivo depletion of CD8+ T cells delayed, but did not prevent tumor rejection. Adoptively transferred TIL mediated swift rejection of intraocular tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specific CTL activity that was demonstrable in vitro. The results strongly suggest, but do not prove, that TIL mediate rejection of intraocular tumors from transgenic mice by direct cytolysis. Although CD4+ T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8+ CTL.

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