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Impaired cytotoxic T lymphocyte response to Epstein‐Barr virus‐infected NK cells in patients with severe chronic active EBV infection
Author(s) -
Tsuge Ikuya,
Morishima Tsuneo,
Kimura Hiroshi,
Kuzushima Kiyotaka,
Matsuoka Hiroshi
Publication year - 2001
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1029
Subject(s) - ctl* , cytotoxic t cell , immunology , epstein–barr virus , biology , virus , virology , t cell , adoptive cell transfer , immune system , cd8 , in vitro , biochemistry
Clinical evidence of a relationship between severe chronic active Epstein‐Barr virus (EBV) infection and clonal expansion of EBV‐infected T or NK cells has been accumulated. In order to clarify pathogenesis of EBV‐infected cell proliferation in patients with severe chronic active EBV infection, cytotoxic T lymphocyte (CTL) responses of two patients against B‐lymphoblastoid cell lines (B‐LCL) and EBV‐infected NK cells were examined in comparison with those of HLA‐identical healthy siblings. Unexpectedly, patients' CTL activities induced by mixed culture with autologous B‐LCLs were markedly reduced, although uncontrolled EBV‐related B‐cell proliferations have never been experienced. In contrast, limiting dilution analysis demonstrated that B‐LCL‐specific CTL precursor (CTLp) frequencies of patients were comparable to those of their healthy sisters. The existence of normal levels of B‐LCL‐specific T cell responses was confirmed by flow‐cytometric analysis of IFN‐γ‐producing T cells after stimulation with B‐LCLs. Infected NK‐cell‐specific CTLp frequencies of the patients were at undetectable levels despite their expression of latent membrane protein (LMP) 1, suggesting mechanisms to escape immunologic surveillance. In the patients' HLA‐identical healthy sisters, infected NK‐cell‐specific CTLps were detected, and infected NK‐cell‐specific CTL clones could be established. From these findings, two treatment options for severe chronic active EBV infection are offered for consideration: adoptive transfer of in vitro‐cultured CTL, and bone marrow transplantation from HLA‐identical donors. J. Med. Virol. 64:141–148, 2001. © 2001 Wiley‐Liss, Inc.