PMID- 21042237
OWN - NLM
STAT- MEDLINE
DCOM- 20110128
LR  - 20111117
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 12
DP  - 2010 Dec 27
TI  - Quantitative and functional diversity of cross-reactive EBV-specific CD8+ T cells 
      in a longitudinal study cohort of lung transplant recipients.
PG  - 1439-49
LID - 10.1097/TP.0b013e3181ff4ff3 [doi]
AB  - BACKGROUND: Cross-reactive antiviral memory T cells constitute a significant 
      proportion of the alloresponse, potentially playing a pivotal role in adverse 
      posttransplant outcomes in human leukocyte antigen (HLA)-mismatched allografts. 
      We explored the longitudinal dynamics of cross-reactive HLA-B8-restricted 
      Epstein-Barr virus-specific CD8+ T cells directed toward the EBNA3A epitope 
      FLRGRAYGL (FLR) in lung transplant recipients (LTRs) to determine whether their 
      corecognition of HLA-B*4402 expressed on the allograft contributed to poorer 
      posttransplant outcomes. METHODS: Cross-reactive FLR-specific CD8+ T cells were 
      measured in the peripheral blood mononuclear cells and bronchoalveolar lavage 
      fluid in 11 HLA-B8+ LTR, who had received HLA-B44+ lung allograft, after in vitro 
      autologous (FLR pulsed) or allogeneic stimulation by multiparameter flow 
      cytometry. RESULTS: FLR-specific CD8+ T cells were detectable ex vivo and after 
      13 days following in vitro peptide stimulation of peripheral blood mononuclear 
      cells. Individual LTR and demonstrated diverse functional profiles of either 
      cytokine production and/or cytotoxic potential (interferon-g+, 
      interferon-g+CD107a+ and CD107a+ subsets). However, cells isolated from 
      bronchoalveolar lavage exhibited a skewed functional phenotype toward CD107a 
      expression alone, indicating cytotoxic-producing but not cytokine-producing 
      capabilities. In addition, our findings suggested that the presence of 
      cross-reactive FLR-specific CD8+ T cells may influence the alloreactive hierarchy 
      directed against the allograft, although they were not associated with poorer 
      short- or long-term clinical outcomes in the absence of Epstein-Barr virus 
      reactivation and in the setting of current immunosuppression and antiviral 
      prophylaxis protocols. CONCLUSION: We report, for the first time, the 
      longitudinal measurement of cross-reactive FLR-specific CD8 T cells within a 
      clinical transplantation framework.
FAU - Mifsud, Nicole A
AU  - Mifsud NA
AD  - Department of Medicine, Monash University, Central Clinical School, The Alfred 
      Hospital, Melbourne, Victoria, Australia. nicole.mifsud@monash.edu
FAU - Nguyen, Thi Hoang Oanh
AU  - Nguyen TH
FAU - Tait, Brian D
AU  - Tait BD
FAU - Kotsimbos, Tom C
AU  - Kotsimbos TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (DNA, Viral)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B44 Antigen)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (Isoantigens)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - B-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line
MH  - Cohort Studies
MH  - Cross Reactions
MH  - DNA, Viral/blood
MH  - Epstein-Barr Virus Infections/*immunology
MH  - Genetic Variation
MH  - HLA-B Antigens/immunology
MH  - HLA-B44 Antigen
MH  - HLA-B8 Antigen/immunology
MH  - Herpesvirus 4, Human/*genetics/immunology
MH  - Humans
MH  - Immunologic Memory
MH  - Isoantigens/immunology
MH  - Lung Transplantation/*immunology
MH  - Receptors, Antigen, T-Cell/immunology
MH  - T-Lymphocyte Subsets/immunology
MH  - Transplantation, Homologous/immunology
EDAT- 2010/11/03 06:00
MHDA- 2011/02/01 06:00
CRDT- 2010/11/03 06:00
PHST- 2010/11/03 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
AID - 10.1097/TP.0b013e3181ff4ff3 [doi]
PST - ppublish
SO  - Transplantation. 2010 Dec 27;90(12):1439-49. doi: 10.1097/TP.0b013e3181ff4ff3.