CD4⁺ T-cell-dependent tumour rejection in an immune-privileged environment requires macrophages

Although intraocular tumours reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection. Ocular tumour rejection typically follows one of two pathways. One pathway involves CD4⁺ T cells, delayed-type hypersensitivity (DTH), and culmination in ischemic necrosis of the tumour and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized tumour, Ad5E1, to investigate the role of CD4⁺ T cells in the non-phthisical form of intraocular tumour rejection. It has been previously documented that CD4 ⁺ T cells and interferon (IFN)-γ are necessary for rejection of these tumours in the eye. In this study, we demonstrate that CD4⁺ T cells can circumvent immune privilege and infiltrate intraocular Ad5E1 tumours. Following tumour rejection, CD4⁺ T cells from tumour rejector mice could be adoptively transferred to severe combined immunodeficiency (SCID) mice and protect them from intraocular Ad5E1 tumour growth. Tumour-specific CD4 ⁺ T cells produced IFN-γ in response to Ad5E1 tumour antigens. Macrophages also contributed to rejection, as they were present in intraocular Ad5E1 tumours, and local depletion of macrophages resulted in progressive tumour growth. Ocular macrophages contributed to Ad5E1 tumour rejection, as Ad5E1 tumour rejection did not occur in macrophage-depleted SCID mice reconstituted with rejector CD4⁺ T cells. This demonstrates that macrophage and CD4⁺ T-cell co-operation is needed for non-phthisical rejection of intraocular tumours.