title: Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency.
abstract: Common variable immunodeficiency (CVI) is a syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and increased occurrence of both autoimmune disease and malignancy. In our study we examine the expression of lymphokine genes in mitogen-activated T cells from four patients with CVI. T cells from patients with CVI did not differ significantly from normals in total T cell number, CD4/CD8 ratio, CD45R expression, or proliferation in response to PHA. However, T cells from this group of patients did exhibit significant abnormalities of mitogen-induced lymphokine gene expression. T cells from patients exhibited significantly decreased expression of IL-2, IL-4, IL-5, and IFN-gamma when compared to normal controls. In contrast to these abnormal findings, mitogen-activated T cells from patients with CVI expressed normal amounts of IL-2R alpha and c-myc suggesting that these patients have a selective abnormality of T cell activation. Furthermore, it is likely that the deficient production of IFN-gamma by patient T cells is partially due to the abnormality of IL-2 production as the levels of IFN-gamma mRNA detected during the initial IL-2-independent phase of T cell activation were normal and the addition of exogenous rIL-2 was able to normalize IFN-gamma production by PHA-stimulated patient cells. Finally, supernatants from PHA-activated cultures of patients PBMC were deficient in their ability to support Ig secretion by Staphylococcus A Cowan's-activated normal B cells suggesting that these T cell abnormalities may contribute to the pathogenesis of this syndrome.
authors.affiliation: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: M C
authors.initials: MC
authors.lastname: Sneller
authors.forename: W
authors.initials: W
authors.lastname: Strober
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D015848:Interleukin-5; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma