title: Defective CD2 T cell pathway activation in common variable immunodeficiency (CVID).
abstract: Clonal T cell expansion requires simultaneous activation of the TCR and secondary signals, e.g. CD2, CD4, CD28. Interference of CD2/CD58 interaction with MoAbs abrogates the primary immune response and antibody production. Given this functional importance of CD2/CD58 interaction for the generation of specific immune responses, we demonstrate for the first time a defective CD2 pathway activation in patients with CVID (seven children and four adults). The costimulatory effect of monocytes upon CD2-triggered proliferation was significantly impaired in CVID patients: 4.080 ct/min versus 20.769 ct/min in controls (P < 0.05). Second, IL-1, which is a strong comitogenic factor for activation via CD2 in normal T cells, showed a defective amplifier function of the CD2 pathway in most patients (median 1.714 ct/min in patients versus 17.521 ct/min in controls; P < 0.05). In addition, by using a mitogenic combination of CD2 plus CD45 MoAb, median proliferation of T cells was severely depressed in patients: 10.577 ct/min versus 34.685 ct/min in controls (P = 0.005). In conclusion, the marked dysfunction seen in responsiveness to phytohaemagglutinin (PHA) (median 24.594 ct/min in patients versus 52.229 ct/min in controls; P < 0.001) and after CD2 triggering, together with the unaffected response to TCR-CD3, suggest that the T cell deficiency in CVID is in part due to deficiencies in the CD2 pathway. Since direct activation of protein kinase C(PKC) by phorbol ester restores defective T cell responses to normal, our results suggest that an early signal-transducing defect might exist at a step proximal to PKC activation in patients with CVID.
authors.affiliation: Department of Paediatrics, J.W. Goethe-Universität Frankfurt, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zielen
authors.forename: T J
authors.initials: TJ
authors.lastname: Dengler
authors.forename: P
authors.initials: P
authors.lastname: Bauscher
authors.forename: S C
authors.initials: SC
authors.lastname: Meuer
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007375:Interleukin-1; D011971:Receptors, Immunologic; D011493:Protein Kinase C