title: Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia.
abstract: Idiopathic CD4(+) lymphocytopenia (ICL) is defined by a stable loss of CD4(+) T cells in the absence of any known cause of immune deficiency. This syndrome is still of undetermined origin. It affects adult patients, some of them displaying opportunistic infections similar to HIV-infected subjects. The hypothesis that the cellular immune defect may be due to biochemical failures of the CD3-TCR pathway is investigated here in a patient associating a severe selective CD4(+) lymphocytopenia with an increased CD8(+) T cell count discovered in the course of a cryptococcal meningitidis. A 40% reduction of T cell proliferation to CD3-TCR stimulation is observed only in the CD4(+) subpopulation. The early CD3-induced protein tyrosine phosphorylations are conserved in both CD4(+) and CD8(+) subsets, and the levels of the T cell protein tyrosine kinases p56(Lck), p59(Fyn) and ZAP-70 are normal. However, we find a 50% reduction of p56(Lck) kinase activity in the patient's T cells compared to a healthy control donor. p59(Fyn) activity does not appear to be altered. Nevertheless, we do not find any genetic abnormality of p56(Lck). These results thus suggest that a defect of an unknown protein regulating p56(Lck) activity takes place in this patient's T cells. Taken together, these findings reveal p56(Lck) alteration in ICL and confirm the critical role of this kinase in the maintenance of the peripheral CD4(+) T cell subpopulation.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, CNRS UMR 7627, CHU Pitié-Salpétrière, 83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
authors.forename: P
authors.initials: P
authors.lastname: Hubert
authors.forename: F
authors.initials: F
authors.lastname: Bergeron
authors.forename: V
authors.initials: V
authors.lastname: Ferreira
authors.forename: M
authors.initials: M
authors.lastname: Seligmann
authors.forename: E
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: P
authors.initials: P
authors.lastname: Debre
authors.forename: B
authors.initials: B
authors.lastname: Autran
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000172:deficiency* / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000201:enzymology* / Q000276:immunology
chemical_list: D017252:CD3 Complex; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019000:Phosphotyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)