Aberrant T-cell receptor signalling of interferon-γ-and tumour necrosis factor-α-producing cytotoxic CD8+ Vδ1/Vβ16 T cells in a patient with chronic neutropenia

I. Bank, L. Cohen, A. Kneller, N. K. De Rosbo, M. Book, A. Ben-Nun

Research output: Contribution to journalArticlepeer-review

Abstract

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 VδS1/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.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalScandinavian Journal of Immunology
Volume58
Issue number1
DOIs
StatePublished - 1 Jul 2003

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