title: An imbalance of naive and memory/effector subsets and altered expression of CD38 on T lymphocytes in two girls with hyper-IgM syndrome.
abstract: In this report we evaluated CD4(+) T, CD8(+) T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4(+) T lymphocyte population, expression of CD38 on T lymphocytes, and CD4(+) and CD8(+) T cell cytokine production in two girls with hyper-IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4(+) T cell counts were low in both children (patient 1: 214 cells/mm(3) and patient 2: 392 cells/mm(3)), and the CD4/CD8 T cell ratio was 0.4 for patient 1, the patient with the more severe disease, and 1.4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm(3)) and borderline (286 cells/mm(3)) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA(+) 27(+) (naive) CD4(+) T lymphocytes being 5.8 and 12.4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in CD4(+) and CD8(+) T lymphocytes upon PMA-Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4(+) T lymphocytes and a dramatic redistribution of naive and memory/effector CD4(+) T lymphocytes in two girls with non-X-linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.
authors.affiliation: Division of Allergy, Clinical Immunology and Rheumatology of the Department of Pediatrics, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: B T
authors.initials: BT
authors.lastname: Costa-Carvalho
authors.forename: M A
authors.initials: MA
authors.lastname: Viana
authors.forename: M K C
authors.initials: MK
authors.lastname: Brunialti
authors.forename: E G
authors.initials: EG
authors.lastname: Kallas
authors.forename: R
authors.initials: R
authors.lastname: Salomao
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis*; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D007371:Interferon-gamma / Q000032:analysis; D007424:Intracellular Fluid / Q000737:chemistry; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1