Recovery of Activated Cytotoxic T Cells from Minor H Incompatible Tumor Graft Rejection Sites

Abstract

In this study we determined whether minor H-specific cytotoxic T cells and their precursors (_PT_c) are present at the site of rejection of minor H disparate tumor allografts. Lymphocytes were retrieved from eyes of BALB/c mice that received sub-conjunctival injections of minor H-incompatible P815 tumor cells. The lymphocytes were then assayed for direct cytotoxic activity as well as precursor frequency by limiting dilution. Similar assays were conducted on cells obtained from the draining lymph nodes and from the spleen. As expected, tumor rejection was accompanied by significant clonal expansion of minor H-specific _PT_c within the draining lymph node and the spleen. A correspondingly high frequency of _PT_c was also detected at the graft site. More importantly, fully functional cytotoxic T cells were recovered from the tumor graft site during rejection, but no similarly active cells were found in either the draining nodes or spleen. We conclude that, after Ag stimulation, _PT_c are generated in draining central lymphoid compartments. From this generative site, the precursor cells then disseminate systemically, gradually reaching and infiltrating the tumor graft site. A further activation step, dependent upon Ag and T cell help, permits these cells to mature into fully active cytotoxic cells which can then effect tumor rejection. We propose that the terminal stage(s) of _PT_c activation is promoted by lymphokines released locally from T_DH cells that are also generated during the alloimmune response and simultaneously infiltrate the site.

Abbreviations used in this paper
Tc,	=	cytotoxic T cell;
PTc,	=	precursors of cytotoxic T cells;
TDH.	=	T cells that mediate delayed hypersensitivity;
pi,	=	postinoculation.

Abbreviations used in this paper
Tc,	=	cytotoxic T cell;
PTc,	=	precursors of cytotoxic T cells;
TDH.	=	T cells that mediate delayed hypersensitivity;
pi,	=	postinoculation.