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Preferential Th1 profile of T helper cell responses in X-linked (Bruton′s) agammaglobulinemia

✍ Scribed by Amedeo Amedei; Chiara Romagnani; Marisa Benagiano; Annalisa Azzurri; Federico Fomia; Franco Torrente; Alessandro Plebani; Mario M. D'Elios; Gianfranco Del Prete


Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
96 KB
Volume
31
Category
Article
ISSN
0014-2980

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✦ Synopsis


X-linked agammaglobulinemia (XLA) is a primary immunodeficiency of the B-cell compartment caused by a defective gene encoding for the tyrosine kinase (btk) essential for B cell differentiation. Affected males undergo recurrent pyogenic infections and deficient immunoglobulin production. Peripheral blood T cells from 6 XLA patients and 6 matched healthy controls were stimulated with either PHA or tetanus toxoid (TT) and T cell clones obtained were compared for their cytokine profile. In the series of PHA-induced or TT-specific CD4 + T cell clones derived from XLA patients, the Th1 profile was predominant (63 and 65 %, respectively). Upon stimulation with TT, the proportion of activated T cells from XLA that expressed the IFN-+ -associated LAG-3 activation molecule was higher than in control T cells (51 vs. 25 %), whereas the expression of the IL-4-associated CD30 molecule was lower (5 vs. 21 %). In a cohort of 31 XLA patients, plasma levels of soluble (s)LAG-3 and sCD30, chosen as indirect indicators of the Th1/Th2 activity in vivo, were significantly higher and lower, respectively, than those measured in 31 healthy controls. Likewise, plasma levels of interferon-inducible protein 10 and of macrophage-derived chemokine in XLA patients were significantly higher and lower, respectively, than in healthy controls.