PMID- 30320878
OWN - NLM
STAT- MEDLINE
DCOM- 20190522
LR  - 20190522
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 48
IP  - 12
DP  - 2018 Dec
TI  - During acute graft versus host disease CD28 deletion in donor CD8(+) , but not 
      CD4(+) , T cells maintain antileukemia responses in mice.
PG  - 2055-2067
LID - 10.1002/eji.201847669 [doi]
AB  - Donor lymphocyte infusions together with allogeneic hematopoietic stem cell 
      transplantation are routinely used as second-line treatment for hematological 
      malignancies. Mature T cells in the graft crucially mediate a graft versus 
      leukemia (GvL) response, but also attack healthy tissues in the recipient leading 
      to potentially life-threatening acute graft versus host disease. Using inducible 
      CD28 knockout C57BL/6 mice as T-cell donors, we have now assessed whether CD28 
      costimulation of donor CD4(+) and/ or CD8(+) T cells is required for an efficient 
      GvL effect after allogeneic T-cell transplantation into BALB/c recipients. Our 
      results show that CD28 costimulation of donor CD8(+) cytotoxic, but not CD4(+) 
      helper, T cells was dispensable for curing mice from the BCL-1 lymphoma. 
      Therefore, donor lymphocyte infusion treated lymphoma-bearing BALB/c recipient 
      mice showed enhanced long-term survival when receiving CD28-deficient as compared 
      to wild-type donor CD8(+) T cells together with wild-type conventional and 
      regulatory CD4(+) T cells. The same was observed when donor CD8(+) and 
      conventional and regulatory CD4(+) T cells were CD28 deficient. Our data, thus, 
      suggest that systemic CD28 blockade, for example, with the drug FR104 might also 
      reduce acute graft versus host disease in patients after allogeneic hematopoietic 
      stem cell transplantation, while maintaining the protective GvL response.
CI  - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Uri, Anna
AU  - Uri A
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Luhder, Fred
AU  - Luhder F
AD  - Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical 
      Center Gottingen, Gottingen, Germany.
FAU - Kerkau, Thomas
AU  - Kerkau T
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Beyersdorf, Niklas
AU  - Beyersdorf N
AUID- ORCID: 0000-0002-9236-5415
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181114
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CD28 Antigens)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - CD28 Antigens/genetics/*metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology/transplantation
MH  - CD8-Positive T-Lymphocytes/*immunology/transplantation
MH  - Cells, Cultured
MH  - Cyclin D1/genetics
MH  - Disease Models, Animal
MH  - Graft vs Host Disease/*immunology
MH  - Graft vs Leukemia Effect/*immunology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Lymphocyte Transfusion
MH  - Lymphoma/*immunology/therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Tissue Donors
MH  - Transplantation, Homologous
OTO - NOTNLM
OT  - Acute graft versus host disease
OT  - CD28 costimulation
OT  - CD4+ T cells
OT  - CD8+ T cells
OT  - Graft versus leukemia effect
EDAT- 2018/10/16 06:00
MHDA- 2019/05/23 06:00
CRDT- 2018/10/16 06:00
PHST- 2018/04/27 00:00 [received]
PHST- 2018/08/02 00:00 [revised]
PHST- 2018/10/09 00:00 [accepted]
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2019/05/23 06:00 [medline]
PHST- 2018/10/16 06:00 [entrez]
AID - 10.1002/eji.201847669 [doi]
PST - ppublish
SO  - Eur J Immunol. 2018 Dec;48(12):2055-2067. doi: 10.1002/eji.201847669. Epub 2018 
      Nov 14.