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Göteborgs universitets publikationer

ADP-ribosylation control the outcome of tolerance or enhanced priming following mucosal immunization.

Författare och institution:
Annemarie Hasselberg (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Lena Ekman (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Linda Fahlén-Yrlid (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Karin Schön (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Nils Y Lycke (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi)
Publicerad i:
Journal of Immunology, 184 ( 6 ) s. 2776-2784
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Accumulating evidence suggests that the dichotomy between tolerance and active IgA immunity in mucosal immune responses is regulated at the APC level. Therefore, immunomodulation of the APC could be an effective mechanism to control the two response patterns. In this study, we demonstrate that ADP-ribosylation controls the outcome of tolerance or active effector T cell immunity to an internal peptide p323–339 from OVA inserted into the cholera toxin (CT)-derived CTA1-OVA-DD adjuvant. We found that a single point mutation, CTA1R7K-OVA-DD, resulting in lack of enzymatic activity, promoted peptide-specific tolerance in TCR transgenic CD4+ T cells following a single intranasal (i.n.) treatment. The CTA1R7K-OVA-DD–induced tolerance was strong, long-lasting, and impaired the ability of adoptively transferred naive peptide-specific CD4+ T cells to respond to Ag-challenge, irrespective if this was given i.p or i.n. The tolerance correlated with induction of regulatory T cells of the regulatory T type 1 characterized by CD25−Foxp3−CD4+ T cells producing IL-10. In contrast, in IL-10–deficient mice, no peptide-specific tolerance was observed, and these mice exhibited unimpaired CD4+ T cell responsiveness to recall Ag irrespective of if they were untreated (PBS) or treated i.n. with CTA1R7K-OVA-DD. Thus, for the first time, we can provide unequivocal proof that ADP-ribosylation can control the outcome of mucosal Ag exposure from tolerance to an enhanced effector CD4+ T cell response. The exploitation of this system for clinical treatment of autoimmune diseases is discussed.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Mikrobiologi inom det medicinska området
Postens nummer:
Posten skapad:
2010-01-22 08:14
Posten ändrad:
2011-09-26 12:04

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