Journal
BLOOD
Volume 128, Issue 17, Pages 2165-2174Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-06-718619
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Funding
- Erasmus Medical Center Translational Research program
- Dutch Cancer Society [UL 2008-4263]
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Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4(+) T-cell numbers rapidly increase after dUCBT, and early CD4(+) T-cell chimerism predicts for graft predominance. Given the frequent HLA class II allele mismatches between CBUs in dUCBT, we hypothesized that alloreactive HLA class II-specific CD4(+) T cells from the winning CBU may contribute to rejection of the loser CBU. We evaluated whether CD4(+) T cells originating from the predominant (PD)-CBU would recognize HLA class II allele mismatches, expressed by the nonengrafting (NE)-CBU. Alloreactive effector CD4(+) T cells toward 1 or more mismatched HLA class II alleles of the NE-CBU were detected in 11 of 11 patients, with reactivity toward 29 of 33 (88%) tested mismatches, and the strongest reactivity toward DR and DQ alleles early after dUCBT. Mismatched HLA class II allele-specific CD4(+) T cells recognized primary leukemic cells when the mismatched HLA class II allele was shared between NE-CBU and patient. Our results suggest that cytotoxicity exerted by CD4(+) T cells from the PD-CBU drives the rapid rejection of the NE-CBU, whose alloreactive effect might also contribute to graft-versus-leukemia.
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