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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3127-3139
Survival of Donor Leukocyte Subpopulations in Immunocompetent
Transfusion Recipients: Frequent Long-Term Microchimerism in Severe
Trauma Patients
Tzong-Hae Lee,
Teresa Paglieroni,
Hitoshi Ohto,
Paul V. Holland, and
Michael P. Busch
From Research and Scientific Services, Blood Centers of the Pacific
(formerly Irwin Memorial Blood Centers), San Francisco, CA; Sacramento
Medical Foundation Blood Centers, Sacramento, CA; Fukushima Medical
College, Fukushima, Japan; the Department of Internal Medicine,
University of California Davis Medical Center, Sacramento, CA; and the
Department of Laboratory Medicine, University of California, San
Francisco, CA.
We recently reported detection of a transient increase in
circulating donor leukocytes (WBCs) in immunocompetent
recipients 3 to 5 days posttransfusion (tx) (Blood 85:1207,
1995). We have now characterized survival kinetics of specific donor
WBC subsets in additional tx populations. Eight female elective surgery
patients (pts) were sampled pre-tx and on days 1, 3, 5, 7, and 14 post-tx. Ten female trauma pts transfused with a total of 4 to 18 U of relatively fresh red blood cells were sampled up to 1.5 years post-tx.
WBC subsets from frozen whole blood were isolated using CD4, CD8 (T
cell), CD15 (myeloid), and CD19 (B cell) antibody-coated magnetic
beads. Donor WBCs were counted by quantitative polymerase chain
reaction (PCR) of male-specific sex determining region (SRY) sequences.
PCR HLA typing and mixed leukocyte reaction (MLR) between recipient and
donor WBCs were performed on two of the trauma tx recipients who had
long-term chimerism of donor cells post-tx. In 6 of 8 female surgery
pts, circulating CD4+ male donor cells peaked at day 3 or
5 (0.01 to 1 cell/µL), followed by clearance by day 14. In 7 of 10 female trauma pts, we observed multilineage persistence of male donor
WBCs (CD4, CD8, CD15, CD19) for 6 months to 1.5 years
post-tx at concentrations of 10 to 100 cells/µL. In 2 trauma
recipients studied, MLR showed no, or very low, response to WBC of the
single donor implicated as the source of microchimerism by HLA typing.
Establishment of long-term multilineage chimerism in trauma recipients
is probably caused by engraftment of donor stem cells and mutual
tolerance between recipient and donor leukocytes. A better
understanding of factors determining clearance versus chimerism of
transfused leukocytes is critical to prevention of alloimmunization and
transfusion-induced graft-versus-host disease, and, potentially, to
induction of tolerance for transplantation.
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