A wide spectrum of different immunologic abnormalities have been postulated as being responsible for the impairment of specific antibody production and the decrease in all or selected immunoglobulin isotypes present in common variable immunodeficiency (CVID). These abnormalities include impaired B cell differentiation and/or function, defective macrophage function, and significant T cell defects. The aim of the present study was to delineate whether the accessory molecule CD28 is involved in the impaired antigen response of T cells from patients with CVID. Our results demonstrate that CD28 costimulation was functional in T cells stimulated with anti-CD3 or anti-TCR MoAb, but could not correct the impaired response of patients' peripheral blood T cells to tetanus toxoid. Analysis of patients' long-term cultured T cells further confirmed these results. Exogenous rIL-2, another costimulus, augmented but did not correct the defective proliferation and lymphokine production in patients' antigen-driven peripheral blood T lymphocytes or in long-term cultured T cells. These findings indicate that the CD28 signalling pathway in these patients' T cells is unimpaired, and that costimulation via CD28 cannot correct the defect occurring in the course of TCR-mediated T cell activation.

• MeSH
• aktivace lymfocytů * MeSH
• antigeny CD28 * fyziologie   MeSH
• běžná variabilní imunodeficience * imunologie   MeSH
• dospělí MeSH
• interleukin-2 biosyntéza   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• monoklonální protilátky imunologie   MeSH
• T-lymfocyty * imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Defects in T cell function are known to be present in a subset of patients with CVID, but the true nature of these defects still has to be revealed. In prior studies we described that T cells from these patients show an impaired proliferative response following activation with recall antigens (E. coli, Tet. Tox., TBE and PPD). Gene expression of IL2 and IFN-gamma in patients' T cells following antigenic stimulation was significantly reduced compared to controls, while IL-2R transcripts were normal. To further characterize the defect we examined T cell responses to bacterial enterotoxins, collectively termed superantigens. Following stimulation with optimal (10 ng/ml p < 0.05) as well as suboptimal (1 ng/ml p < 0.0025) concentrations of staphylococcal enterotoxin A (SEA), proliferative response and cytokine release (IL-2 and IFNg) were significantly decreased in patients' T cells as compared to controls'. When patients' T cells were stimulated with staph. enterotox. C3 (SEC3) an even more pronounced difference between patients' and controls' T cells could be observed (10 ng/ml p < 0.002, 1 ng/ml p < 0.0005). Our data indicate that, in addition to the defect in antigen-induced T cell activation, T cells of CVID patients express a broader impairment in the interaction between the antigen presenting cell and the TCR.

• MeSH
• aktivace lymfocytů * MeSH
• antigeny CD3 MeSH
• antigeny aplikace a dávkování   MeSH
• běžná variabilní imunodeficience * imunologie   MeSH
• enterotoxiny imunologie   MeSH
• interferon gama biosyntéza   MeSH
• interleukin-2 biosyntéza   MeSH
• lidé MeSH
• receptory antigenů T-buněk MeSH
• Staphylococcus aureus imunologie   MeSH
• superantigeny aplikace a dávkování   MeSH
• T-lymfocyty * imunologie   MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH