Elevated levels of activated CD4 T cells in common variable immunodeficiency: association with clinical findings.
BACKGROUND
Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The primary defect remains unknown, but many reports describe peripheral blood T and B lymphocyte dysfunctions in a substantial proportion of CVID patients. Immunophenotypic alterations on memory B lymphocytes correlate with clinical findings. A B-cell-oriented classification principle of the patients has been proposed.


RESULTS
We investigated the expression of activation surface molecules on CD4 and CD8 T-cells from 14 patients with CVID, 6 non-CVID hypogammaglobulinemic patients with recurrent infections, 47 asymptomatic HIV-positive patients without AIDS defining conditions and 23 healthy subjects. Lymphocyte subsets were analysed by three-colour flow cytometry. Monoclonal panel: CD38-FITC/HLADR-PE/CD4 or CD8-PerCP. In CVID patients serum levels of CD4 T-cells co-expressing the activation marker HLA-DR [CD4+DR+ (34 %), CD4+CD38+DR+ (18 %)] were significantly elevated compared with controls. Significant increases in CD8+DR+ (54%), CD8+ CD38+ (43%) and CD8+CD38+DR+ (29%) T-cells were observed in comparison with healthy controls. CVID patients with splenomegaly, lower pre-infusion IgG levels (< 600 mg/dl), autoimmune or lymphoproliferative conditions demonstrated even higher levels of CD4+CD38+DR+T cells (22, 22, 21 and 21% respectively) compared with other CVID patients (13, 13, 15 and 15% respectively).


CONCLUSIONS
These findings indicate a state of ongoing T lymphocyte activation which is associated with clinical findings frequently observed in CVID.
Carbone
J
J
Immunology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain. carbone@teleline.es
Sarmiento
E
E
Micheloud
D
D
Rodríguez-Molina
J
J
Fernández-Cruz
E
E
D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000150:complications / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008297:Male; D008875:Middle Aged; D013163:Splenomegaly / Q000209:etiology
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007074:Immunoglobulin G