[Study on the attenuation of graft versus host disease by methoxy polyethylene glycol modification of donor lymphocytes].
OBJECTIVE
To find out why mPEG modification of donor's lymphocytes can attenuate the occurrence of graft versus host disease(GVHD), but not affect the hemopoietic reconstitution of stem/progenitor cells after transplanting the mPEG-modified mononuclear cells from human cord blood into the SCID mice.


METHODS
The followings were observed: (1) Changes of CD4(+) and CD8(+) T cells and the ratio of CD4(+)/CD8(+) T cells were examined by flow cytometry before and after mononuclear cells from human cord blood were modified with mPEG. (2) The difference in forming the CFU-GM in-vitro between the mPEG modified-stem/progenitor cell group and non-modified cell group was observed. (3) The time of appearance of GVHD and the survival of the SCID mice were observed after the pre- and post-modification mononuclear cells were transplanted. (4) The number of humanized CD45(+) cells in the mouse's bone marrow was detected about 7 weeks after transplantation.


RESULTS
(1) mPEG nearly completely covered up the CD4 and CD8 antigens on T cells, while the number of CFU-GM did not show any obvious change between the modified and non-modified cell groups. (2) GVHD appeared later in the modified mononuclear cell group than in the non-modified group, and the survival rate was elevated in the modified group than in the non-modified group. (3) Humanized CD45 cells were found in mouse's bone marrow at the 47th day after transplantation of both mPEG-modified and non-modified mononuclear cells.


CONCLUSIONS
After CD4 and CD8 antigens were covered up with mPEG, the graft's immune response against host was weakened, but the proliferation and differentiation of transplanted hemopoietic stem/progenitor cells were not affected.
Zhang
Quan
Q
Department of Obstetrics and Gynecology, PLA General Hospital, Beijing 100853, China. Zhang301h@hotmail.com
Yuan
Yi
Y
Li
Su-Bo
SB
Dou
Na
N
Ma
Fu-Ling
FL
Ji
Shou-Ping
SP
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects*; D014183:Transplantation, Heterologous
D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D017493:Leukocyte Common Antigens