PMID- 12352893
OWN - NLM
STAT- MEDLINE
DCOM- 20021023
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 74
IP  - 5
DP  - 2002 Sep 15
TI  - Characterization of cytotoxic function of CMV-pp65-specific CD8+ T-lymphocytes 
      identified by HLA tetramers in recipients and donors of stem-cell transplants.
PG  - 722-32
AB  - BACKGROUND: Human cytomegalovirus (CMV) is a ubiquitous herpesvirus that is an 
      important complication of bone marrow and allogeneic stem-cell transplant (HSCT). 
      CD8 T-lymphocytes have an important role in immunity against CMV, but correlation 
      between antigen-specific subpopulations of these cells and protection are still 
      unclear. METHODS: Flow analysis with fluorescently-conjugated human leukocyte 
      antigen (HLA) class I tetramers (Tet) was used to investigate levels of 
      CMV-specific CD8 T-lymphocytes in peripheral blood monocyte cells (PBMC) samples 
      from HSCT donors and recipients and their ability to produce interferon 
      (IFN)-gamma on stimulation with either CMV antigenic peptide or nonspecific 
      mitogenic stimulation. Chromium release assays were used to evaluate ex vivo 
      CMV-specific cytotoxicity associated with the PBMC samples. RESULTS: Use of Tet 
      in conjunction with fluorescently conjugated anti-T-cell receptor (TCR) 
      beta-chain variable (Vbeta) monoclonal antibodies indicated that the Vbeta 
      repertoires associated with Tet cells seen in two HSCT recipients were similar to 
      the Vbeta repertoires of the Tet cells in their HSCT donors. Significant ex vivo 
      cytotoxicity against peptide-loaded targets was measured from several recipient 
      samples after transplant. However, PBMC from the HSCT donors, even when 
      containing populations of CMV-specific Tet cells capable of secreting IFN-gamma 
      in response to peptide stimulation, possessed no ex vivo CMV-specific 
      cytotoxicity. CONCLUSIONS: We hypothesize that in the setting of the 
      reconstituting immune system of HSCT recipients, CMV reactivation may stimulate a 
      functional change in CMV-specific CD8 T-lymphocytes, rendering them able to 
      directly lyse target cells presenting CMV antigens without in vitro stimulation. 
      These findings have important implications for development of vaccines designed 
      to induce protective cellular immunity to CMV in transplant recipients.
FAU - Lacey, Simon F
AU  - Lacey SF
AD  - Laboratory of Vaccine Research, Division of Virology, Beckman Research Institute 
      of the City of Hope, Duarte, California 91010, USA. slacey@coh.org
FAU - Gallez-Hawkins, Ghislaine
AU  - Gallez-Hawkins G
FAU - Crooks, Matthew
AU  - Crooks M
FAU - Martinez, Joybelle
AU  - Martinez J
FAU - Senitzer, David
AU  - Senitzer D
FAU - Forman, Stephen J
AU  - Forman SJ
FAU - Spielberger, Ricardo
AU  - Spielberger R
FAU - Zaia, John A
AU  - Zaia JA
FAU - Diamond, Don J
AU  - Diamond DJ
LA  - eng
GR  - CA33572/CA/NCI NIH HHS/United States
GR  - M01 RR-43/RR/NCRR NIH HHS/United States
GR  - P01-CA30206/CA/NCI NIH HHS/United States
GR  - R01-AI43267/AI/NIAID NIH HHS/United States
GR  - R01-CA77544/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (cytomegalovirus matrix protein 65kDa)
RN  - 0R0008Q3JB (Chromium)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Chromium/pharmacokinetics
MH  - Cytomegalovirus/genetics/*immunology/isolation & purification
MH  - *Cytotoxicity, Immunologic
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Major Histocompatibility Complex
MH  - Phosphoproteins/*immunology
MH  - Polymerase Chain Reaction
MH  - Receptors, Antigen, T-Cell, alpha-beta/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tissue Donors
MH  - Viral Matrix Proteins/*immunology
EDAT- 2002/09/28 04:00
MHDA- 2002/10/31 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - 10.1097/00007890-200209150-00023 [doi]
PST - ppublish
SO  - Transplantation. 2002 Sep 15;74(5):722-32. doi: 10.1097/00007890-200209150-00023.