Publication details
A DEFECT IN THE EARLY PHASE OF T-CELL RECEPTOR-MEDIATED T-CELL ACTIVATION IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY
| Authors | |
|---|---|
| Year of publication | 1994 |
| Type | Article in Periodical |
| Magazine / Source | BLOOD |
| MU Faculty or unit | |
| Citation | |
| Field | Immunology |
| Keywords | HUMAN B CELLS; PROLIFERATIVE RESPONSES; INTERFERON GAMMA; GENE EXPRESSION; INTERLEUKIN 2; HYPOGAMMAGLOBULINEMIA; IL 2; ANTIGEN; DIFFERENTIATION; ABNORMALITIES |
| Description | 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 leg, 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 [SEI); however, T-cell response to mitogens (anti-CD3 monoclonal antibody, phytohemagglutinin) was normal. The defect in interleukin-2 and interferon-gamma release on tetanus toroid 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. |