| Autor: |
Mizrahi, Mark, Cal, Pablo, Rosenthal, Martin, Ochayon, David, Shahaf, Galit, Kaner, Ziv, Kachker, Peter, Lewis, Eli C. |
| Předmět: |
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| Zdroj: |
Immunology; Nov2013, Vol. 140 Issue 3, p362-373, 12p |
| Abstrakt: |
B-lymphocyte activities are associated with allograft rejection. Interleukin-10 (IL-10) -expressing B cells, however, exhibit regulatory attributes. Human α1-antitrypsin (h AAT), a clinically available anti-inflammatory circulating glycoprotein that rises during acute-phase responses, promotes semi-mature dendritic cells and regulatory T (Treg) cells during alloimmune responses. Whether B lymphocytes are also targets of h AAT activity has yet to be determined. Here, we examine whether h AAT modulates B-cell responses. In culture, h AAT reduced the lipopolysaccharide-stimulated Ki-67+ B-cell population, Ig M release and surface CD40 levels, but elevated IL-10-producing cells 1.5-fold. In CD40 ligand-stimulated cultures, h AAT promoted a similar trend; reduction in the Ki- 67+ B-cell population and in surface expression of CD86, CD80 and MHCII. hAAT increased interferon-γ-stimulated macrophage B-cell activating factor ( BAFF) secretion, and reduced BAFF-receptor levels. Draining lymph nodes of transgenic mice that express circulating h AAT ( C57 BL/6 background) and that received skin allografts exhibited reduced B-lymphocyte activation compared with wild-type recipients. BSA-vaccinated h AAT transgenic mice exhibited 2.9-fold lower BSA-specific Ig G levels, but 2.3-fold greater IgM levels, compared with wild-type mice. Circulating Treg cells were 1.3-fold greater in transgenic h AAT mice, but lower in B-cell knockout ( BKO) and chimeric h AAT- BKO mice, compared with wild-type mice. In conclusion, B cells are cellular targets of h AAT. hAAT-induced Treg cell expansion appears to be B-cell-dependent. These changes support the tolerogenic properties of h AAT during immune responses, and suggest that h AAT may be beneficial in pathologies that involve excessive B-cell responses. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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