title: T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections.
abstract: Common variable immunodeficiency disorders (CVID) are a group of heterogeneous conditions that have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X-linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four-colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup. There was a reduction in early differentiated CD4 and CD8 T cells and increased CD8 TEM in the CVID patients, particularly autoimmune cytopenia and polyclonal lymphoproliferation subgroups, suggesting a more activated T cell phenotype, due perhaps to an antigen-driven process. XLA patients had significantly reduced putative follicular T cells, which may depend on B cells for survival, while no significant alterations were observed in the T cells of those with IgG subclass deficiency or selective IgA deficiency.
authors.affiliation: Department of Clinical Laboratory Immunology, Churchill Hospital Clinical Immunology, John Radcliffe Hospital, Oxford, UK.
authors.forename: E A L
authors.initials: EA
authors.lastname: Bateman
authors.forename: L
authors.initials: L
authors.lastname: Ayers
authors.forename: R
authors.initials: R
authors.lastname: Sadler
authors.forename: M
authors.initials: M
authors.lastname: Lucas
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: A
authors.initials: A
authors.lastname: Woods
authors.forename: K
authors.initials: K
authors.lastname: Packwood
authors.forename: J
authors.initials: J
authors.lastname: Burden
authors.forename: D
authors.initials: D
authors.lastname: Harrison
authors.forename: N
authors.initials: N
authors.lastname: Kaenzig
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: H M
authors.initials: HM
authors.lastname: Chapel
authors.forename: B L
authors.initials: BL
authors.lastname: Ferry
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C515370:CCR7 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054400:Receptors, CCR7