title: Impaired selective cytokine production by CD4(+) T cells in Common Variable Immunodeficiency associated with the absence of memory B cells.
abstract: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by B cell dysfunction and decreased serum immunoglobulin. CVID patients are classified by the absence or presence of memory B cells. In addition, T cell defects have been demonstrated in only a proportion of CVID patients. The aim of this study was to evaluate the function of CD4(+) T cells from CVID patients and its association with memory B cells. Patients were classified according to their Freiburg groups: group Ia and Ib, with decreased switched memory B cells (<0.4 of PBL), and group II, with normal B cell subsets. Their T cell function was evaluated after stimulation. We observed normal and even increased CD4(+) T cell proliferation in group Ia (p=0.0277). The proliferation positively correlated with the clinical severity score (r=0.4796). We observed lower levels of IL-17A and IL-10 in group Ia (p=0.0177, 0.0109) and Ib (p=0.0009, 0.0084) patients. Group Ib patients also had low levels of IL-13 and IL-9 (p=0.0169, 0.010). Group II patients had similar cytokine production to that of the controls. BAFFR expression was reduced in groups Ia (p=0.0001) and Ib (p=0.0002) and showed an inverse correlation with the severity score (p=0.0262; r=0.5371). ICOS expression was reduced in group Ia (p=0.0364), and PD-1 was increased in group Ib (p=0.0432) patients. This study shows a selective impairment in cytokine production in group Ia patients, which was more extensive than in group Ib patients. The impairment was associated with BAFFR expression in B cells, with ICOS and PD-1 in T cells and, remarkably, with the absence of memory B cells and with the disease severity. Our results suggest that the evaluation of cytokine expression by T cells in combination with the study of B cell memory could be important for understand the pathogenesis of CVID patients.
authors.affiliation: Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría SSa, Av. Insurgentes Sur # 3700-C, Colonia Insurgentes Cuicuilco, México, D.F, México.
authors.forename: Laura
authors.initials: L
authors.lastname: Berrón-Ruiz
authors.affiliation: Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría SSa, Av. Insurgentes Sur # 3700-C, Colonia Insurgentes Cuicuilco, México, D.F, México.
authors.forename: Gabriela
authors.initials: G
authors.lastname: López-Herrera
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, IPN,, Av. Instituto Politécnico Nacional # 2508, Colonia Zacatenco, 07360 México, D.F, México.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vargas-Hernández
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, IPN,, Av. Instituto Politécnico Nacional # 2508, Colonia Zacatenco, 07360 México, D.F, México.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional (CMN) Siglo XXI. Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc 330, Col. Doctores, C.P. 06720 México, D.F, México.
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional (CMN) Siglo XXI. Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc 330, Col. Doctores, C.P. 06720 México, D.F, México.
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.affiliation: Servicio de Alergia e Inmunología Clínica, Hospital de Especialidades CMN, Siglo XXI, IMSS, Av. Cuauhtémoc 330, Col. Doctores, C.P. 06720 México, D.F, México.
authors.forename: Nora Hilda
authors.initials: NH
authors.lastname: Segura-Méndez
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional (CMN) Siglo XXI. Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc 330, Col. Doctores, C.P. 06720 México, D.F, México. Electronic address: labonifaz@yahoo.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonifaz
mesh_terms: D000328:Adult; D000368:Aged; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D053265:B-Cell Activation Factor Receptor; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556692:ICOS protein, human; C508609:IL10 protein, human; C578095:IL13 protein, human; C508717:IL17A protein, human; C508607:IL9 protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D018793:Interleukin-13; D020381:Interleukin-17; D016906:Interleukin-9; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C435926:TNFRSF13C protein, human; D016753:Interleukin-10
keywords: Activation; Co-stimulation; Common variable immunodeficiency; Cytokine; Memory B cells; T helper cells