Journal
SCIENCE
Volume 368, Issue 6495, Pages 1122-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aax4040
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Funding
- NIH [AI145881, AI080779, AI099465]
- Frank and Athena Sarris Chair in Transplantation Biology at the University of Pittsburgh
- JDRF
- Canadian Institutes of Health Research
- SickKids Foundation
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Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired imrnunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes.
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