| Autor: |
Nikolic, Tatjana, Suwandi, Jessica S., Wesselius, Joris, Laban, Sandra, Joosten, Antoinette M., Sonneveld, Petra, Mul, Dick, Aanstoot, Henk-Jan, Kaddis, John S., Zwaginga, Jaap Jan, Roep, Bart O. |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 11/22/2022, Vol. 13, p01-13, 13p |
| Abstrakt: |
Introduction: Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production in-vitro, providing an appealing immunotherapy to intervene in autoimmune disease progression. Methods: A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry. Results: The tolDC vaccine induced a profound and durable decline in preexisting autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS+CCR4+TIGIT+ Tregs and CD103+ tissue-resident and CCR6+ effector memory CD4+ T-cells increased in response to the first tolDC injection, the latter declining thereafter below baseline levels. Discussion: Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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