Cornelia Weyand

Publication Details

  • IL-7-and IL-15-Mediated TCR Sensitization Enables T Cell Responses to Self-Antigens JOURNAL OF IMMUNOLOGY Deshpande, P., Cavanagh, M. M., Le Saux, S., Singh, K., Weyand, C. M., Goronzy, J. J. 2013; 190 (4): 1416-1423

    Abstract:

    Regulation of the ERK pathway is intimately involved in determining whether TCR stimulation is productive or induces anergy. T cells from patients with rheumatoid arthritis (RA) have increased ERK responsiveness, which may be relevant for disease pathogenesis. Inflammatory cytokines such as TNF-? did not reproduce the TCR hypersensitivity typical for RA in T cells from healthy individuals. In contrast, priming with the homeostatic cytokines (HCs) IL-7 and IL-15 amplified ERK phosphorylation to TCR stimulation 2- to 3-fold. The underlying mechanism involved a priming of the SOS-dependent amplification loop of RAS activation. The sensitization of the TCR signaling pathway has downstream consequences, such as increased proliferation and preferential Th1 differentiation. Importantly, priming with IL-7 or IL-15 enabled T cell responses to autoantigens associated with RA. Production of HCs is induced in lymphopenic conditions, which have been shown to predispose for autoimmunity and which appear to be present in the preclinical stages of RA. We propose that HCs, possibly induced by lymphopenia, decrease the signaling threshold for TCR activation and are thereby partly responsible for autoimmunity in RA.

    View details for DOI 10.4049/jimmunol.1201620

    View details for Web of Science ID 000314825400005

    View details for PubMedID 23325887

Stanford Medicine Resources:

Footer Links: