Local T helper cell signals by lymphocytes infiltrating intraocular tumors

Tumor-infiltrating lymphocytes from mice bearing minor histoincompatible tumor cells in the anterior chamber (AC) or subconjunctival (SCon) space of the eye have been shown to contain large numbers of tumor-specific precursor cytotoxic T cells. Because SCon tumors eventually acquire directly cytotoxic, tumor-specific T cells and are rejected by their hosts and because AC tumors never acquire cytotoxic effector cells and are not rejected, we have examined tumor-infiltrating lymphocytes from both types of ocular tumors for the capacity to secrete lymphokines in response to in vitro stimulation with tumor cells. The results indicate that T "helper" cells were able to infiltrate both SCon and AC tumors. In the former, T cells capable of secreting IL-2 and IL-4 were found whereas in the latter only IL-2-secreting T cells were detected. These findings implicate a defect in local delivery of appropriate T cell help as the reason why AC tumors are not rejected. The failure of AC tumor-bearing mice to destroy their tumors correlates not only with defective delivery of local help but with a systemic inability to produce tumor-specific T cells that can secrete IL-2 and IL-4. Because these mice also generate down-regulatory T cells that suppress the expression of tumor-specific delayed hypersensitivity, they appear to have an immunologically mediated block in T helper cell differentiation which renders them unable to generate either T helper 1 or T helper 2 cells. This immunologic abnormality is discussed in terms of tumor rejection and the phenomenon of immunologic privilege.