title: Defective interleukin-2 and interferon-gamma gene expression in response to antigen in a subgroup of patients with common variable immunodeficiency.
abstract: Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and in the underlying mechanisms leading to the immunodeficiency. The impairment of B-cell function can be due to an intrinsic defect of the B cells, a deficiency in the function of the antigen-presenting cell, or a dysfunction in the course of T-cell activation. In the present report we have focused our attention on T-lymphocyte activation in three patients with CVID. Numbers of T and B cells, as well as CD4 and CD8 T cell subsets, were within the normal range. The patients' B cells secreted IgM but did not secrete IgG and IgA in response to B-cell stimuli in vitro. Addition of allogeneic T cells was followed by an increase in IgM production but had no effect on the other immunoglobulin isotypes. Examination of T-cell function revealed impaired proliferative response, interleukin-2 (IL-2) and interferon-gamma gene expression and IL-2 release after antigenic stimulation, whereas T-cell proliferation, as well as IL-2 gene expression and release in response to stimulation via anti-CD3, were comparable to those of healthy control subjects. Anti-CD3-induced IFN-gamma gene activation in T cells from two patients was comparable to that of control subjects, whereas T cells from the third patient showed reduced expression of IFN-gamma mRNA. In contrast to the decreased IL-2 and IFN-gamma mRNA levels, IL-2R transcripts examined in parallel were normal in CVID T cells on stimulation with antigen. The defect in IL-2 and IFN-gamma mRNA expression after stimulation with antigen, but not with anti-CD3, suggests an abnormality confined to T-cell activation by the T-cell receptor.
authors.affiliation: Institute of Immunology, University of Vienna, Austria.
authors.forename: M B
authors.initials: MB
authors.lastname: Fischer
authors.forename: I
authors.initials: I
authors.lastname: Hauber
authors.forename: E
authors.initials: E
authors.lastname: Vogel
authors.forename: H M
authors.initials: HM
authors.lastname: Wolf
authors.forename: J W
authors.initials: JW
authors.lastname: Mannhalter
authors.forename: M M
authors.initials: MM
authors.lastname: Eibl
mesh_terms: D000328:Adult; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; D007136:Immunoglobulins; D007376:Interleukin-2; D008222:Lymphokines; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma