Purchase this article with an account.
K.C. McKenna, J.A. Kapp; Immunosuppressive CD11b+ Myeloid Cells Accumulate Within the Eye During Tumor Growth in the Anterior Chamber . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5162.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ocular immune privilege is exemplified by the observation that weakly immunogenic tumors grow progressively when injected into the anterior chamber (a.c.) of the eye of mice but are rejected by CD8+ CTL responses when injected into the skin. Herein, our purpose was to elucidate mechanisms of immune evasion by primary ocular tumors to better understand CD8+ CTL inhibition to ocular antigens.
E.G7–OVA tumors expressing chicken ovalbumin (OVA) as a surrogate tumor antigen, were injected into the a.c. of C57Bl/6 (B6).Pl, B6.Rag–/– and OT–I mice or injected intradermally (i.d.) into the skin of B6, B6.Rag–/–, B6.B2M–/–, and B6.CD4–/– mice and tumor growth was monitored. OVA–specific cytolytic activity was measured in mice given E.G7–OVA i.d. Ocular tumor infiltrating leukocytes (CD45+) were analyzed for CD8, CD11b, and GR–1 expression. CD11b+ leukocytes isolated from ocular tumors or naïve spleens were added to cytolytic T lymphocyte (CTL) cultures and lytic activity was measured.
OVA–specific CD8+ CTL eliminated limiting numbers of E.G7–OVA injected into the skin but not in the a.c. of B6 mice. E.G7–OVA grew progressively in the eye despite the induction of tumor–specific immune responses that eliminated a subsequent injection of E.G7–OVA in the opposite eye. CD8+ T cells were not detected in primary ocular tumors but were present in eyes of mice previously primed with E.G7–OVA in the a.c. that rejected a subsequent challenge of E.G7–OVA in the opposite eye. E.G7–OVA tumors were eliminated when injected into the a.c. of TCR transgenic OT–I mice in which CD8+ T cells express an OVA–specific TCR suggesting that that tumor–specific CD8+ CTL can migrate into primary ocular tumors. E.G7–OVA tumors did not lose antigenicity or become immune–suppressive after growth in the eye. CD11b+ cells accumulated in primary ocular tumors and suppressed the development of CTL responses in vitro.
Immunosuppressive CD11b+ myeloid cells accumulate within the eye as tumors develop in the a.c. and may contribute to immune evasion by primary ocular tumors by inhibiting CTL within the tumor microenvironment.
This PDF is available to Subscribers Only