A radiosensitive APC activity dissociates IL-2 secretion and activation-induced cell death by autoreactive T cell hybridomas

Shiv A. Prasad, Steven P. Fling, Dale S. Gregerson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


T cell hybridomas were generated from a LEW rat T cell line specific for the uveltogenic 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 γ-irradiation. Although the co-stimulation-blocking reagent CTLA-4-Ig mimicked the effect of γ-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 thirdparty 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.

Original languageEnglish (US)
Pages (from-to)1787-1798
Number of pages12
JournalInternational Immunology
Issue number11
StatePublished - Nov 1995

Bibliographical note

Funding Information:
This work was supported in part by NIH grants R01-EY09207 and T32 EY07133, Research to Prevent Blindness, Inc., and the Minnesota Lions and Lionesses Clubs. D. S. G. is an RPB Senior Scientific Investigator. We thank Dr Marc Jenkins for providing CTLA-4-lg and the B7.C1 cells, Drs Dan Gold and Tomas Hunig for the R73 mAb, and Michael Hupke and Lisa Kamp for flow cytometry analysis.


  • Autoimmunity
  • EAU
  • Radiosensitivity
  • S-antigen
  • Tolerance


Dive into the research topics of 'A radiosensitive APC activity dissociates IL-2 secretion and activation-induced cell death by autoreactive T cell hybridomas'. Together they form a unique fingerprint.

Cite this