PMID- 14702534
OWN - NLM
STAT- MEDLINE
DCOM- 20040121
LR  - 20171116
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 76
IP  - 11
DP  - 2003 Dec 15
TI  - CD8-interaction mutant HLA-Cw3 molecules protect porcine cells from human natural 
      killer cell-mediated antibody-dependent cellular cytotoxicity without stimulating 
      cytotoxic T lymphocytes.
PG  - 1615-22
AB  - BACKGROUND: CD56+ human natural killer (NK) cells are the principal anti-pig 
      cytotoxic effectors in vitro. Expression of certain human leukocyte antigen (HLA) 
      class I molecules in porcine cells can inhibit NK cell-mediated natural 
      cytotoxicity in serum-free medium, but had not been shown to inhibit 
      antibody-dependent cellular cytotoxicity (ADCC) by CD16+ NK cells in the presence 
      of human xenoreactive immunoglobulin G. Moreover, expression of HLA molecules 
      might amplify the previously weak CD8+ cytotoxic T-lymphocyte (CTL) response 
      against porcine cells. METHODS: A novel porcine B-lymphoblastoid cell line 
      (13271) was stably transfected with HLA-Cw*0304 gene constructs encoding 
      wild-type (wt) Cw3 or genetically modified Cw3 unable to interact with CD8 
      (Cw3-D227K). The Cw3 transfectants were used in limiting dilution assays to 
      estimate the CTL precursor frequency in CD56-depleted human peripheral blood 
      mononuclear cells (PBMC) obtained from eight unrelated donors. The 13271 
      transfectants were also used as targets for clonal and polyclonal NK cells in the 
      presence and absence of human serum, to measure inhibition of ADCC. RESULTS: 
      Expression of Cw3-wt in 13271 cells significantly increased the human CTL 
      response compared with the empty-vector control transfectant, whereas no 
      significant increase resulted from expression of CD8-interaction mutant Cw3-D227K 
      molecules. The Cw3-D227K mutant was indistinguishable from Cw3-wt in its ability 
      to inhibit both natural cytotoxicity and ADCC mediated by human NK clones that 
      have the appropriate CD158b inhibitory receptor. CONCLUSIONS: Transgenic 
      expression of HLA molecules in pig cells will likely amplify the CD8+ CTL 
      response against the xenograft. Disruption of HLA-CD8 interaction could minimize 
      this amplification without compromising NK-cell inhibition.
FAU - Sharland, Alexandra
AU  - Sharland A
AD  - Laboratory of Molecular and Cellular Immunology, Department of Surgery, 
      Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
FAU - Lee, Josie Han
AU  - Lee JH
FAU - Saidman, Susan
AU  - Saidman S
FAU - Waneck, Gerald L
AU  - Waneck GL
LA  - eng
GR  - AI43440/AI/NIAID 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 (CD8 Antigens)
SB  - IM
MH  - Animals
MH  - Antibody-Dependent Cell Cytotoxicity/*immunology
MH  - CD8 Antigens/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation
MH  - Swine
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2004/01/02 05:00
MHDA- 2004/01/22 05:00
CRDT- 2004/01/02 05:00
PHST- 2004/01/02 05:00 [pubmed]
PHST- 2004/01/22 05:00 [medline]
PHST- 2004/01/02 05:00 [entrez]
AID - 10.1097/01.TP.0000086342.60603.C2 [doi]
PST - ppublish
SO  - Transplantation. 2003 Dec 15;76(11):1615-22. doi: 
      10.1097/01.TP.0000086342.60603.C2.