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Publication : Unlinked memory helper responses promote long-lasting humoral alloimmunity.

First Author  Conlon TM Year  2012
Journal  J Immunol Volume  189
Issue  12 Pages  5703-12
PubMed ID  23162131 Mgi Jnum  J:190849
Mgi Id  MGI:5449791 Doi  10.4049/jimmunol.1202257
Citation  Conlon TM, et al. (2012) Unlinked memory helper responses promote long-lasting humoral alloimmunity. J Immunol 189(12):5703-12
abstractText  Essential help for long-lived alloantibody responses is theoretically provided only by CD4 T cells that recognize target alloantigen, processed and presented by the allospecific B cell. We demonstrate that in an alloresponse to multiple MHC disparities, cognate help for class-switched alloantibody may also be provided by CD4 T cells specific for a second "helper" alloantigen. This response was much shorter-lived than when help was provided conventionally, by Th cell recognition of target alloantigen. Nevertheless, long-lasting humoral alloimmunity developed when T cell memory against the helper alloantigen was first generated. Costimulatory blockade abrogated alloantibody produced through naive Th cell recognition of target alloantigen but, crucially, blockade was ineffective when help was provided by memory responses to the accessory helper alloantigen. These results suggest that memory Th cell responses against previously encountered graft alloantigen may be the dominant mechanism for providing help to generate new specificities of alloantibody in transplant patients receiving immunosuppression.
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