CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation.
The recently proposed Piqueras classification of common variable immunodeficiency (CVID) patients is based on flow cytometric quantification of IgD class-switched and CD27 membrane-expressing mature blood B cells. But, many patients also have circulating T cells with immunophenotypic abnormalities, often associated with clinical complications, such as splenomegaly, autoimmune disease, lymphoid proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets according to their expression of HLA-DR and intracellular perforin and/or granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte percentages, predominantly CD8+DR+, were significantly higher in patients with clinical complications. MB0 classified patients, characterized by fewer CD27+ B cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical complications and showed no signs of T-cell activation. MB1 patients (normal CD27+ numbers but fewer IgD- B cells) were either clinically normal or had complications. Combining the set of markers described herein might better define homogeneous groups of patients for etiological studies and clearly segregate patients with clinical complications.
Viallard
Jean-François
JF
Department of Internal Medicine and Infectious Diseases, Haut-Lévêque Hospital, 5, avenue Magellan, 33604 Pessac, France. jean-francois.viallard@chu-bordeaux.fr
Blanco
Patrick
P
André
Marc
M
Etienne
Gabriel
G
Liferman
François
F
Neau
Didier
D
Vidal
Elisabeth
E
Moreau
Jean-François
JF
Pellegrin
Jean-Luc
JL
D000293:Adolescent; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000032:analysis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D017074:Common Variable Immunodeficiency / Q000145:classification / Q000276:immunology* / Q000473:pathology; D005260:Female; D053804:Granzymes; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000473:pathology
D018941:Antigens, CD19; C515370:CCR7 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D054353:Perforin; D017493:Leukocyte Common Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases