Role of IL-12 in Intrathymic Negative Selection

  • Lúdvíksson B
  • Ehrhardt R
  • Strober W
24Citations
Citations of this article
13Readers
Mendeley users who have this article in their library.

Abstract

Cytokines are central regulatory elements in peripheral lymphocyte differentiation, but their role in T cell ontogeny is poorly defined. In the present study, we evaluated the role of IL-12 in thymocyte selection more directly by determining its role in two models of in vivo negative selection. In initial studies we demonstrated that abundant intrathymic IL-12 synthesis occurs during OVA peptide-induced negative selection of thymocytes in neonatal OVA-TCR transgenic mice, and such synthesis is associated with increased IL-12R β2-chain expression as well as STAT4 intracellular signaling. In further studies, we showed that this form of negative selection was occurring at the αβTCRlowCD4lowCD8low stage and was prevented by the coadministration of anti-IL-12. In addition, the IL-12-dependent thymocyte depletion was occurring through an intrathymic apoptosis mechanism, also prevented by administration of anti-IL-12. Finally, we showed that IL-12 p40−/− mice displayed aberrant negative selection of double positive CD4+CD8+ thymocytes when injected with anti-CD3 mAb. These studies suggest that intact intrathymic IL-12 production is necessary for the negative selection of thymocytes occurring in relation to a high “self” Ag load, possible through its ability to induce the thymocyte maturation and cytokine production necessary for such selection.

Cite

CITATION STYLE

APA

Lúdvíksson, B. R., Ehrhardt, R. O., & Strober, W. (1999). Role of IL-12 in Intrathymic Negative Selection. The Journal of Immunology, 163(8), 4349–4359. https://doi.org/10.4049/jimmunol.163.8.4349

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free