Failure of infiltrating precursor cytotoxic T cells to acquire direct cytotoxic function in immunologically privileged sites.

Minor H incompatible P815 tumor cells inoculated into the anterior chamber (AC) of the eyes of BALB/c mice grow progressively, revealing this to be an immunologically privileged site. By contrast, a similar inoculation of tumor cells is rapidly rejected from nonprivileged ocular sites (subconjunctiva). Mice with progressively growing AC-tumors and those that reject their ocular subconjunctiva tumors both have expanded clones of tumor-specific cytotoxic precursor cells (pTc) in their spleens and cervical lymph nodes. In an effort to determine why the expanded pool of primed pTc is unable to effect rejection of AC intraocular tumors, we have examined the susceptibility of the tumor cells growing within the immunologically privileged AC to lysis by cytotoxic T cells and the cytotoxic function of tumor-infiltrating lymphocytes. P815 tumor cells extracted from intraocular tumors and P815 cells maintained in routine tissue culture are equally susceptible to lysis when exposed in vitro to fully differentiated, DBA/2-specific cytotoxic T cells. Thus, progressively growing tumor cells within the AC are not insensitive to immune-mediated lysis by cytotoxic T cells. We have been able to harvest significant numbers of DBA/2-specific pTc from these same intraocular tumors. When the tumor-infiltrating lymphocytes are driven in vitro with exogenous IL-2, they acquire the capacity to lyse specifically P815 tumor cells. However, no evidence of fully cytotoxic, tumor-specific T cells was found among lymphocytes harvested from intraocular tumors, i.e., when the harvested cells were tested immediately for cytolytic activity. Inasmuch as we have reported that directly cytotoxic T cells are present during tumor rejection at nonimmunologically privileged ocular sites, such as the subconjunctival space, we conclude that progressive growth of P815 tumor cells within the anterior chamber is due in part to a failure of infiltrating pTc to differentiate in situ into fully functional cytotoxic effector cells.