title: Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID).
abstract: The proliferative responses of T lymphocytes of a subset of patients with CVID are abnormally low. This may be due to abnormalities in extracellular interactions or signalling defects downstream from membrane-associated receptors. Demonstrating that the T cell receptor signalling was normal, we observed no abnormal pattern of activation-induced tyrosine phosphorylation in cells from CVID patients. Moreover, the addition of exogenous IL-2 increased the low proliferation to mitogens, thus indicating the integrity of the IL-2R signalling apparatus. Attractin is a rapidly expressed T cell activation antigen involved in forming an association between T cells and monocytes. Twenty-four to 48 h after activation by CD3 cross-linking, attractin expression was not up-regulated on the cells of CVID patients despite normal up-regulation of CD25 and CD26. On control cells, however, attractin expression was up-regulated together with CD25 and CD26. The addition of the purified 175-kD attractin was capable of restoring the proliferative response of peripheral blood mononuclear cells following CD3 X-L in the presence of suboptimal concentrations of rIL-2 (10 and 20 U/ml). The effect was dose-dependent with the maximal effect at a concentration of 500 ng/ml, and present at a concentration as low as 50 ng/ml. Due to the likely role of attractin in cell guidance and amplification of the immune response, our results indicate that the lack of up-regulation of the molecule in patients with CVID may in turn affect any further step of productive immune response. Our finding may also imply a potential therapeutic role for this novel molecule.
authors.affiliation: Department of Paediatrics and Immunohaematology Unit, Federico II University, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Pozzi
authors.forename: L
authors.initials: L
authors.lastname: Gaetaniello
authors.forename: B
authors.initials: B
authors.lastname: Martire
authors.forename: D
authors.initials: D
authors.lastname: De Mattia
authors.forename: B
authors.initials: B
authors.lastname: Balestrieri
authors.forename: E
authors.initials: E
authors.lastname: Cosentini
authors.forename: S F
authors.initials: SF
authors.lastname: Schlossman
authors.forename: J S
authors.initials: JS
authors.lastname: Duke-Cohan
authors.forename: C
authors.initials: C
authors.lastname: Pignata
mesh_terms: D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000096:biosynthesis; D015415:Biomarkers; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002648:Child; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000172:deficiency* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006023:Glycoproteins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018819:Dipeptidyl Peptidase 4