title: Cytotoxic T-cell-mediated defense against infections in human liver transplant recipients.
abstract: 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.
authors.affiliation: Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Takada
authors.forename: Kazue
authors.initials: K
authors.lastname: Ozawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teramukai
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Masako
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Kenji
authors.initials: K
authors.lastname: Takai
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000328:Adult; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D007239:Infections / Q000276:immunology / Q000401:mortality*; D017493:Leukocyte Common Antigens / Q000032:analysis; D016031:Liver Transplantation; D011183:Postoperative Complications / Q000276:immunology / Q000401:mortality*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D017493:Leukocyte Common Antigens