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Cytotoxic T‐cell‐mediated defense against infections in human liver transplant recipients
Author(s) -
Tanaka Koichi,
Uemoto Shinji,
Egawa Hiroto,
Takada Yasutsugu,
Ozawa Kazue,
Teramukai Satoshi,
Kasahara Mureo,
Ogawa Kohei,
Ono Masako,
Sato Hiroshi,
Takai Kenji,
Fukushima Masanori,
Inaba Kayo
Publication year - 2007
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21065
Subject(s) - cytotoxic t cell , downregulation and upregulation , cd8 , immunology , perforin , t cell , c c chemokine receptor type 7 , cytolysis , cd28 , medicine , transplantation , granzyme b , biology , immune system , in vitro , chemokine , biochemistry , chemokine receptor , gene
Previous studies have shown that postoperative infection is highest in transplant recipients with preexisting high levels of cytotoxic T lymphocytes (CTLs). To study this phenomenon, 106 adult liver transplant recipients were divided into 3 groups, based on hierarchical clustering of the CD3 + CD8 + CD45 isoform fractions prior to living donor liver transplantation (LDLT). Group I had the highest naive T‐cell levels (subset CD45RO − CCR7 + ), Group II had the highest effector/memory (EM) T‐cell levels (subset CD45RO + CCR7 − ), and Group III had the highest effector T‐cell levels (subset CD45RO − CCR7 − ). In Group I, CTLs upregulated in response to invading pathogens much earlier and more rapidly than the other groups; this response was associated with CD4 + T‐cell help, downregulation of CD27 + CD28 + subsets, and upregulation of interferon‐gamma and perforin expression. In contrast, in Groups II and III, CTLs upregulated slowly following persistent viral infection and did not respond efficiently to acute infection. In addition, Group II's cytolytic responses were due mainly to upregulation of the CD8 + EM T‐cell fraction, whereas Group III's cytolytic responses were attributable to upregulation of effector T cells. The prevalence of EM or effector T cells was dependent on differentiation of the CD8 + phenotype before LDLT. In conclusion, in most infected transplant recipients who died, generation of CD8 + CTLs had been suppressed without associated CD4 + T‐cell help. Liver Transpl 13:287–293, 2007. © 2007 AASLD.