دورية أكاديمية

Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.

التفاصيل البيبلوغرافية
العنوان: Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.
المؤلفون: Ruffin, N., Lantto, R., Pensieroso, S., Sammicheli, S., Hejdeman, B., Rethi, B., Chiodi, F.
المصدر: Journal of Internal Medicine; Nov2012, Vol. 272 Issue 5, p492-503, 12p, 5 Graphs
مصطلحات موضوعية: HIV infections, IMMUNE system, INTERLEUKINS, APOPTOSIS, CHROMOSOMAL translocation, B cells
مستخلص: . Ruffin N, Lantto R, Pensieroso S, Sammicheli S, Hejdeman B, Rethi B, Chiodi F (Karolinska Institutet, Stockholm; and South Hospital, Stockholm, Sweden). Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection. J Intern Med 2012; 272: 492-503. Objectives. Microbial translocation and chronic immune activation were previously shown to be associated with impairment of T cell functions and disease progression during infection with human immunodeficiency virus type-1 (HIV-1); however, their impact on B cell function and number remains unknown. By measuring markers of immune activation and molecules involved in apoptosis regulation, we have evaluated the association between microbial translocation and loss of memory B cells in HIV-1-infected patients. Methods. Markers of activation [the interleukin-21 receptor (IL-21R) and CD38] and apoptosis (Bim, Bcl-2 and annexin V) were measured in B cell subpopulations by multicolour flow cytometry. Levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS), measures of microbial translocation, were determined in plasma. Purified B cells were also exposed in vitro to Toll-like receptor (TLR) ligands. Results. IL-21R expression was higher in cells from HIV-1-infected patients, compared with control subjects, with the highest levels in nontreated patients. An inverse correlation was observed between IL-21R expression and percentages of circulating resting memory (RM) B cells. IL-21R-positive memory B cells were also more susceptible to spontaneous apoptosis and displayed lower levels of Bcl-2. It is interesting that the levels of sCD14, which are increased during HIV-1 infection, were correlated with decreased percentages of RM B cells and high IL-21R expression. In the plasma of HIV-1-infected individuals, a correlation was found between sCD14 and LPS levels. TLR activation of B cells in vitro resulted in IL-21R up-regulation. Conclusions. Microbial translocation and the associated immune activation during HIV-1 infection may lead to high expression levels of the IL-21R activation marker in RM B cells, a feature associated with increased apoptosis and a reduced number of these cells in the circulation. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:09546820
DOI:10.1111/j.1365-2796.2012.02550.x