A radiosensitive APC activity dissociates IL-2 secretion and activation-induced cell death by autoreactive T cell hybridomas.
T cell hybridomas were generated from a LEW rat T cell line specific for the uveitogenic peptide bov-B1 of bovine retinal S-antigen. Using these autoreactive hybridomas, IL-2 production and activation-induced cell death (AICD) were dissociated as outcomes of activation. The self-reactive hybridomas secrete IL-2 and undergo AICD in response to antigen presented by non-irradiated syngeneic splenocytes, whereas antigen presentation by irradiated splenocytes induced only AICD. IL-2 production by a non-self reactive hybridoma was unaffected by irradiation of the APC. Pretreatment of the APC with phorbol ester or lipopolysaccharide and IL-4 protected their ability to induce IL-2 secretion after gamma-irradiation. Although the co-stimulation-blocking reagent CTLA-4-Ig mimicked the effect of gamma-irradiation by preventing IL-2 secretion but not AICD, B7 expression on the APC was not radiosensitive, nor did co-stimulation, provided 'in trans' with a B7-expressing third-party cell, reconstitute antigen-specific hybridoma IL-2 secretion in response to irradiated APC. In summary, the data show that IL-2 secretion and AICD of a self-reactive T cell hybridoma can be dissociated as consequences of TCR occupancy in the presence of a functional co-stimulatory signal. It is proposed that the signals producing these events are transduced through the TCR-CD3 complex alone and reflect the differential outcomes of high- and low-affinity interactions.
Prasad
S A
SA
Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.
Fling
S P
SP
Gregerson
D S
DS
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000528:radiation effects*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects*; D001324:Autoantigens / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D018106:CD28 Antigens / Q000378:metabolism / Q000528:radiation effects; D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D002469:Cell Separation; D004307:Dose-Response Relationship, Radiation; D006825:Hybridomas / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000528:radiation effects*; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D007376:Interleukin-2; D046911:Macromolecular Substances