HUMAN GAMMA-DELTA T-CELLS ARE RESISTANT TO INDUCTION OF ANERGY BUT NOT TO INDUCTION OF CELL-DEATH IN-VITRO

A condition of hyporesponsiveness can be induced in certain mature hum an alpha beta (TCR2) cells relatively easily by their stimulation in t he absence of costimulatory signals (signal 1 alone). This state of '' anergy'' has been implicated in tolerance to self and transplanted org ans as well as tumors and may represent an important regulatory compon ent of immune responsiveness. Little is known about whether the same c ondition applies to ya (TCR1) cells. We therefore undertook to investi gate anergy induction in TCR1 cell clones using several approaches kno wn to induce this state in TCRB cells. First, TCR1 clones were found n ot to be anergized by culture on immobilized CD3 monoclonal antibody ( mAb), while the majority of TCRB clones were anergized. Second, blocki ng of autocrine proliferation (stimulated in TCR1 or TCR2 clones by mi togen in the presence of accessory cells) using CTLA-4-lg, a soluble B 7 family counterreceptor resulted in anergy induction in TCR2 cells bu t not TCR1 cells, although experiments with CHO cells transfected with B7-1 (CD80) genes confirmed that these TCR1 clones were responsive to costimulation with B7. Third, blocking mitogen-induced proliferation with anti-IL 2 receptor antibodies and anti-IL 2 antisera resulted in anergy induction in TCR2 but not TCR1 cells. Fourth, stimulation with the calcium ionophore ionomycin also anergized TCRB but not TCR1 cells . In all four systems, but especially in the latter, stimulation by si gnal 1 alone resulted in high levels of cell death (>50%) which was si milar for both TCR1 and TCRB cells. Therefore, these data may reflect a high level of resistance to tolerance induction (manifested as proli ferative anergy) but not to clonal deletion (manifested as stimulation -dependent cell death) on the part of TCR1 cells. (C) 1995 Academic Pr ess,Inc.