A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is characterized by an impairment of specific antibody production and a decrease in all or selected Ig isotypes. Abnormalities at the level of the B cells, T cells, and antigen-presenting cells have been described. In the present study, we have focused our attention on T-cell activation in CVID. T cells from 15 of 24 patients failed to respond to recall antigens (eg, tetanus toxoid, Escherichia coli). Of these 15 patients, 11 were studied in detail and showed significantly decreased T-cell proliferative responses and/or decreased interleukin-2 and interferon-gamma production on T-cell receptor-mediated stimulation with recall antigens and superantigens (staphylococcal enterotoxins [SE]); however, T-cell response to mitogens (anti-CD3 monoclonal antibody, phytohemagglutinin) was normal. The defect in interleukin-2 and interferon-gamma release on tetanus toxoid stimulation could also be documented in purified CD4 T cells of the patients and was present in patients with high and normal CD8 counts alike. Furthermore, patients' T cells failed to mount a significant elevation in free intracellular calcium (Ca++ flux) in response to superantigen, whereas the response to phorbol myristate acetate and ionomycin, bypassing receptor-mediated signaling, was unimpaired. These results indicate a defect in the early phase of T-cell activation after triggering of the T-cell receptor in a significant subgroup of CVID patients.
Fischer
M B
MB
Institute of Immunology, University of Vienna, Austria.
Hauber
I
I
Eggenbauer
H
H
Thon
V
V
Vogel
E
E
Schaffer
E
E
Lokaj
J
J
Litzman
J
J
Wolf
H M
HM
Mannhalter
J W
JW
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000097:blood; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D008222:Lymphokines; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D007371:Interferon-gamma; D002118:Calcium