Donor WBCs can persist and transiently mediate immunologic function in a murine transfusion model: effects of irradiation, storage, and histocompatibility.
BACKGROUND
Donor WBCs are responsible for numerous transfusion complications, but little is known concerning the natural history of their clearance following transfusion or of their function in the recipient's circulation. A murine transfusion model was developed to investigate the effects of blood component characteristics and histocompatibility on donor WBC survival kinetics and function.


METHODS
To investigate the effects of storage and irradiation, fresh whole blood and blood stored for 1, 2, and 6 weeks at 4 degrees C, all from male C57b (H2K(b)) mice, was transfused to female Balb/c (H2K(d)) mice. To study the effect of histocompatibility, blood was also transfused from C57b mice to Balb/c, FVB, C3H, and SW (outbred) mice. To investigate the xenogeneic setting, blood from humans, rats, and rabbits was transfused to Balb/c mice. Samples were collected weekly after transfusion, and the donor WBCs were analyzed, targeting the Y-chromosome with quantitative PCR. To investigate donor WBC function, dinitrochlorobenzene (DNCB) sensitivity was induced in donor and recipient mice, and the transfusion recipients were observed for hypersensitivity to DNCB.


RESULTS
Donor WBCs had reduced in vivo survival equivalent to their period of storage ex vivo at 4 degrees C. Irradiation of donor blood produced no observable difference in donor WBC survival. Allogeneic male donor WBCs persisted (100-<1 cell/microL) in female Balb/c recipient mice blood over 6 weeks. Donor WBC survival kinetics displayed an early MHC-dependent phase, which was followed by a more rapid phase that was not influenced by donor-recipient MHC differences. All donor WBCs were cleared within 24 to 48 hours. DNCB sensitivity was passed through transfusion, where it was transiently expressed in naive recipients.


CONCLUSIONS
The clearance of donor WBCs in the murine transfusion model is much slower than that in humans. Allogeneic donor WBC clearance may be biphasic, involving MHC-dependent as well as MHC-independent mechanisms. DNCB sensitivity can be transferred transiently to a naive recipient.
Lee
T H
TH
Blood Centers of the Pacific, San Francisco, CA, USA. thlee@qpcr.com
Reed
W
W
Mangawang-Montalvo
L
L
Watson
J
J
Busch
M P
MP
D000818:Animals; D001782:Blood Donors; D001803:Blood Transfusion; D002470:Cell Survival; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011817:Rabbits; D051381:Rats
D006183:H-2 Antigens; C024755:H-2K(K) antigen