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

• Published in: European journal of immunology Vol. 31; no. 6; pp. 1927 - 1934
• Main Authors: Amedei, Amedeo, Romagnani, Chiara, Benagiano, Marisa, Azzurri, Annalisa, Fomia, Federico, Torrente, Franco, Plebani, Alessandro, D'Elios, Mario M., Del Prete, Gianfranco
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.06.2001
• Subjects: Adolescent; Adult; agammaglobulinemia; Agammaglobulinemia - blood; Agammaglobulinemia - genetics; Agammaglobulinemia - immunology; Antigens, CD; Atopy; Autoimmunity; Case-Control Studies; CD4 antigen; Chemokine; Chemokine CCL22; Chemokine CXCL10; Chemokines, CC - blood; Chemokines, CXC - blood; Child; Child, Preschool; Female; g-Interferon; Genetic Linkage; Humans; Ki-1 Antigen - biosynthesis; Ki-1 Antigen - blood; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Lymphocyte Activation Gene 3 Protein; Male; Membrane Proteins - biosynthesis; Membrane Proteins - blood; Th1 Cells - immunology; Th1 / Th2 balance; X Chromosome; X‐linked agammaglobulinemia
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200106)31:6<1927::AID-IMMU1927>3.0.CO;2-D

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‐γ ‐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.