The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome.

Abstract:

:Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.

journal_name

Mech Ageing Dev

authors

Plunkett FJ,Franzese O,Belaramani LL,Fletcher JM,Gilmour KC,Sharifi R,Khan N,Hislop AD,Cara A,Salmon M,Gaspar HB,Rustin MH,Webster D,Akbar AN

doi

10.1016/j.mad.2005.03.006

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

855-65

issue

8

eissn

0047-6374

issn

1872-6216

pii

S0047-6374(05)00069-2

journal_volume

126

pub_type

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