ISSN:
1365-3083
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
We previously found that the peripheral blood (PB) mononuclear cells (MCs) (PBMCs) of a patient with chronic neutropenia contained an expanded population of cytotoxic CD8+ T cells using a variable (V) region δ1 gene product in the T-cell receptor-α (TCR-α) polypeptide [Vδ1-constant(C)α+ T cells]. Sequencing of polymerase chain reaction (PCR) amplification products have now revealed a productive Vδ1/joining (J)αIGRJa03/Cα rearrangement of the TCR-α gene, predominantly associated with a Vβ16/Dβ2.1/Jβ2.1/Cβ2 TCR-β gene, in these cells. Furthermore, we detected a markedly deficient proliferative response of the patient PBMCs to triggering with monoclonal antibodies (MoAbs) to the CD3 molecule, contrasting with a substantial response to the Vβ3, 12, 14, 15, 17 and 20-specific staphylococcal enterotoxin B (SEB) superantigen, suggesting defective TCR-mediated activation of the Vδ1+/Vβ16+ clone. Moreover, whereas triggering of Vδ1– T cells cultured with interleukin-2 (IL-2) by MoAb to the CD3 molecule enhanced proliferation, Vδ1-Cα+ T cells were inhibited by MoAbs to either CD3 or Vδ1. Vδ1-Cα+ T-cell clones spontaneously secrete interferon-γ (IFN-γ) and were further induced to release tumour necrosis factor (TNF-α) when triggered by anti-CD3 plus phorbol ester. Aberrant signalling by the clonotypic TCR together with the functional properties of the CD8+ Vδ1+/Vβ16+ clone may thus contribute to the immunohaematological abnormalities observed in this patient.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1365-3083.2003.01272.x
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