CD28 co-stimulation via tumour-specific chimaeric receptors induces an incomplete activation response in Epstein-Barr virus-specific effector memory T cells

B. Altvater, S. Pscherer, S. Landmeier, V. Niggemeier, H. Juergens, J. Vormoor, C. Rossig

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

15 Citaten (Scopus)

Samenvatting

Expression of tumour antigen-specific chimaeric receptors in T lymphocytes can redirect their effector functions towards tumour cells. Integration of the signalling domains of the co-stimulatory molecule CD28 into chRec enhances antigen-specific proliferation of polyclonal human T cell populations. While CD28 plays an essential role in the priming of naive CD4+ T cells, its contribution to effector memory T cell responses is controversial. We compared the function of the chRec with and without the CD28 co-stimulatory domain, expressing it in peripheral blood T cells or Epstein-Barr virus (EBV)-specific T cell lines. The chimaeric T cell receptors contain an extracellular single-chain antibody domain, to give specificity against the tumour ganglioside antigen GD2. The transduced cytotoxic T lymphocytes (CTL) maintained their specificity for autologous EBV targets and their capacity to proliferate after stimulation with EBV-infected B cells. Intracellular cytokine staining demonstrated efficient and comparable antigen-specific interferon (IFN)-γ secretion by CTL following engagement of both the native and the chimaeric receptor, independent of chimaeric CD28 signalling. Furthermore, tumour targets were lysed in an antigen-specific manner by both chRec. However, while antigen engagement by CD28ζ chRec efficiently induced expansion of polyclonal peripheral blood lymphocytes in an antigen-dependent manner, CD28 signalling did not induce proliferation of EBV-CTL in response to antigen-expressing tumour cells. Thus, the co-stimulatory requirement for the efficient activation response of antigen-specific memory cells cannot be mimicked simply by combining CD28 and ζ signalling. The full potential of this highly cytolytic T cell population for adoptive immunotherapy of cancer requires further exploration of their co-stimulatory requirements.

Originele taal-2Engels
Pagina's (van-tot)447-457
Aantal pagina's11
TijdschriftClinical and Experimental Immunology
Volume144
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - jun. 2006
Extern gepubliceerdJa

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