The T cell response to persistent herpes virus infections in common variable immunodeficiency.
We show that at least half of patients with common variable immunodeficiency (CVID) have circulating CD8(+) T cells specific for epitopes derived from cytomegalovirus (CMV) and/or the Epstein-Barr virus (EBV). Compared to healthy age-matched subjects, more CD8(+) T cells in CVID patients were committed to CMV. Despite previous reports of defects in antigen presentation and cellular immunity in CVID, specific CD4(+) and CD8(+) T cells produced interferon (IFN)-gamma after stimulation with CMV peptides, and peripheral blood mononuclear cells secreted perforin in response to these antigens. In CVID patients we found an association between a high percentage of circulating CD8(+) CD57(+) T cells containing perforin, CMV infection and a low CD4/CD8 ratio, suggesting that CMV may have a major role in the T cell abnormalities described previously in this disease. We also show preliminary evidence that CMV contributes to the previously unexplained severe enteropathy that occurs in about 5% of patients.
Raeiszadeh
M
M
Centre for Immunology, Hampstead Campus, Royal Free and University College Medical School, London, UK.
Kopycinski
J
J
Paston
S J
SJ
Diss
T
T
Lowdell
M
M
Hardy
G A D
GA
Hislop
A D
AD
Workman
S
S
Dodi
A
A
Emery
V
V
Webster
A D
AD
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000821:virology; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology; D006566:Herpesviridae Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma