Characterization of Cells That Suppress the Cytotoxic Activity of T Lymphocytes
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
AbstractTarget cell lysis by sensitized cytolytic T lymphocytes (CTL) may be conveniently quantitated by 51Cr release. By fitting to the formula, P (% specific release) = 100 (1-e-N αt), one obtains α, the relative frequency of CTL in N lymphoid cells. Using a microassay and murine sarcoma target cells, we observed an unexpected decrease in lysis whenever effectors obtained from a graft-vs-host reaction were tested at high concentrations. This inhibition was not observed with CTL generated by an MLC reaction. Inhibition could not be explained by nonspecific mechanical ‘crowding’, reutilization of released isotope, suppression of released from dead target cells, or the particular strain combination and target used. By modifying the formula to allow suppression of CTL by a stochastic cell-cell interaction with a suppressor cell, we found that P = 100 (1-e-N ate- Nγ) adequately fitted the data, where Nγ is proportional to inhibitor content. An 18- to 24-hr incubation at 37°C but not 4°C allowed selective depletion or enrichment of inhibitors; in mixing experiments, both parameters Nαt and Nγ behaved stoichiometrically as independent cellular properties. The inhibitor was resistant to concentrations of anti-T cell (RAMB) serum + complement which killed CTL. A similar inhibitor arose in vivo during an anti-tumour allograft response. The ability to quantitate CTL and inhibitor activities from titration curves provides a technique for studying the identity and mechanism of suppressor cells acting at the effector stage of cell-mediated immunity.
