Preferential Th1 profile of T helper cell responses in X-linked (Bruton's) agammaglobulinemia.
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-gamma -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.
Amedei
A
A
Department of Internal Medicine, University of Florence, Florence, Italy.
Romagnani
C
C
Benagiano
M
M
Azzurri
A
A
Fomia
F
F
Torrente
F
F
Plebani
A
A
D'Elios
M M
MM
Del Prete
G
G
D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD; D016022:Case-Control Studies; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000097:blood; D019743:Chemokines, CXC / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood; D018417:Th1 Cells / Q000276:immunology*; D014960:X Chromosome; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; C515482:CCL22 protein, human; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D000093322:Lymphocyte Activation Gene 3 Protein; C000720328:soluble LAG-3 protein, human; C000720326:Lag3 protein, human