PMID- 11313411
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 166
IP  - 9
DP  - 2001 May 1
TI  - Human cytomegalovirus pp65- and immediate early 1 antigen-specific HLA class 
      I-restricted cytotoxic T cell responses induced by cross-presentation of viral 
      antigens.
PG  - 5695-703
AB  - Dendritic cells (DCs) play a pivotal role in the development of anti-viral CD8(+) 
      CTL responses. This is straightforward if they are directly infected with virus, 
      but is less clear in response to viruses that cannot productively infect DCS: 
      Human CMV (HCMV) shows strain-specific cell tropism: fibroblast (Fb)-adapted 
      laboratory strains (AD169) and recent clinical isolates do not infect DCs, 
      whereas endothelial cell-adapted strains (TB40/E) result in productive lytic DC 
      infection. However, we show here that uninfected DCs induce CD8(+) T cell 
      cytotoxicity and IFN-gamma production against HCMV pp65 and immediate early 1 Ags 
      following in vitro coculture with HCMV-AD169-infected Fbs, regardless of the HLA 
      type of these FBS: CD8(+) T cell stimulation was inhibited by pretreatment of DCs 
      with cytochalasin B or brefeldin A, indicating a phagosome/endosome to cytosol 
      pathway. HCMV-infected Fbs were not apoptotic as measured by annexin V binding, 
      and induction of apoptosis of infected Fbs in vitro did not augment CTL induction 
      by DCs, suggesting a mechanism other than apoptosis in the initiation of 
      cross-presentation. Furthermore, HCMV-infected Fbs provided a maturation signal 
      for immature DCs during coculture, as evidenced by increased CD83 and HLA class 
      II expression. Cross-presentation of HCMV Ags by host DCs enables these 
      professional APCs to bypass some of the evasion mechanisms HCMV has developed to 
      avoid T cell recognition. It may also serve to explain the presence of immediate 
      early 1 Ag-specific CTLs in the face of pp65-induced inhibition of Ag 
      presentation at the level of the infected cell.
FAU - Tabi, Z
AU  - Tabi Z
AD  - Department of Medicine, University of Wales, College of Medicine, Cardiff, United 
      Kingdom. tabiz@cf.ac.uk
FAU - Moutaftsi, M
AU  - Moutaftsi M
FAU - Borysiewicz, L K
AU  - Borysiewicz LK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Viral)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (IE1 protein, cytomegalovirus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (cytomegalovirus matrix protein 65kDa)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 20350-15-6 (Brefeldin A)
RN  - 3CHI920QS7 (Cytochalasin B)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Antigen Presentation/drug effects/genetics
MH  - Antigens, Viral/biosynthesis/genetics/*immunology/metabolism
MH  - Apoptosis/immunology
MH  - Brefeldin A/pharmacology
MH  - Cell Count
MH  - Cell Differentiation/immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytochalasin B/pharmacology
MH  - Cytomegalovirus/genetics/*immunology
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Dendritic Cells/cytology/drug effects/immunology/virology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Fibroblasts/cytology/immunology/virology
MH  - Gene Expression Regulation, Viral/immunology
MH  - Green Fluorescent Proteins
MH  - HLA Antigens/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis/genetics/*immunology
MH  - Immunosuppressive Agents/pharmacology
MH  - Luminescent Proteins/biosynthesis/genetics
MH  - Lymphocyte Activation/drug effects
MH  - Molecular Sequence Data
MH  - Phosphoproteins/*immunology
MH  - Signal Transduction/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology/metabolism/virology
MH  - Viral Matrix Proteins/*immunology
MH  - *Viral Proteins
EDAT- 2001/04/21 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/04/21 10:00
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - 10.4049/jimmunol.166.9.5695 [doi]
PST - ppublish
SO  - J Immunol. 2001 May 1;166(9):5695-703. doi: 10.4049/jimmunol.166.9.5695.