Limiting the amount and duration of antigen exposure during priming increases memory T cell requirement for costimulation during recall

Tamara L. Floyd, Brent H. Koehn, William H. Kitchens, Jennifer M. Robertson, Jennifer A. Cheeseman, Linda Stempora, Christian P. Larsen, Mandy L. Ford

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Donor-reactive memory T cells (Tmem) can play an important role in mediating graft rejection after transplantation. Transplant recipients acquire donor-reactive Tmem not only through prior sensitization with alloantigens but also through previous exposure to environmental pathogens that are cross-reactive with allogeneic peptide-MHC complexes. Current dogma suggests that most, if not all, Tmem responses are independent of the requirement for CD28 and/or CD154/CD40-mediated costimulation to mount a recall response. However, heterogeneity among Tmem is increasingly being appreciated, and one important factor known to impact the function and phenotype of Ag-specific T cell responses is the amount/duration of Ag exposure. Importantly, the impact of Ag exposure on development of costimulation independence is currently unknown. In this study, we interrogated the effect of decreased Ag amount/duration during priming on the ability of donor-reactive Tmem to mediate costimulation blockade-resistant rejection during a recall response after transplantation in a murine model. Recipients possessing donor-reactive Tmem responses that were generated under conditions of reduced Ag exposure exhibited similar frequencies of Ag-specific T cells at day 30 postinfection, but, strikingly, failed to mediate costimulation blockade-resistant rejection after challenge with an OVA-expressing skin graft. Thus, these data demonstrate the amount/duration of Ag exposure is a critical factor in determining Tmem's relative requirement for costimulation during the recall response after transplantation.

Original languageEnglish (US)
Pages (from-to)2033-2041
Number of pages9
JournalJournal of Immunology
Volume186
Issue number4
DOIs
StatePublished - Feb 15 2011

Fingerprint Dive into the research topics of 'Limiting the amount and duration of antigen exposure during priming increases memory T cell requirement for costimulation during recall'. Together they form a unique fingerprint.

Cite this