{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:02:44Z","timestamp":1774378964366,"version":"3.50.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Heterologous immunity is recognized as a significant barrier to transplant tolerance. Whereas it has been established that pathogen-elicited memory T cells can have high or low affinity for cross-reactive allogeneic peptide\u2013MHC, the role of TCR affinity during heterologous immunity has not been explored. We established a model with which to investigate the impact of TCR-priming affinity on memory T cell populations following a graft rechallenge. In contrast to high-affinity priming, low-affinity priming elicited fully differentiated memory T cells with a CD45RBhi status. High CD45RB status enabled robust secondary responses in vivo, as demonstrated by faster graft rejection kinetics and greater proliferative responses. CD45RB blockade prolonged graft survival in low affinity\u2013primed mice, but not in high affinity\u2013primed mice. Mechanistically, low affinity\u2013primed memory CD8+ T cells produced more IL-2 and significantly upregulated IL-2R\u03b1 expression during rechallenge. We found that CD45RBhi status was also a stable marker of priming affinity within polyclonal CD8+ T cell populations. Following high-affinity rechallenge, low affinity\u2013primed CD45RBhi cells became CD45RBlo, demonstrating that CD45RB status acts as an affinity-based differentiation switch on CD8+ T cells. Thus, these data establish a novel mechanism by which CD45 isoforms tune low affinity\u2013primed memory CD8+ T cells to become potent secondary effectors following heterologous rechallenge. These findings have direct implications for allogeneic heterologous immunity by demonstrating that despite a lower precursor frequency, low-affinity priming is sufficient to generate memory cells that mediate potent secondary responses against a cross-reactive graft challenge.<\/jats:p>","DOI":"10.4049\/jimmunol.1500639","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T03:58:40Z","timestamp":1455163120000},"page":"2838-2846","source":"Crossref","is-referenced-by-count":44,"title":["Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity"],"prefix":"10.1093","volume":"196","author":[{"given":"Scott M","family":"Krummey","sequence":"first","affiliation":[{"name":"Emory Transplant Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan J","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakieb","family":"Andargachew","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danya","family":"Liu","sequence":"additional","affiliation":[{"name":"Emory Transplant Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maylene","family":"Wagener","sequence":"additional","affiliation":[{"name":"Emory Transplant Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob E","family":"Kohlmeier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian D","family":"Evavold","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian P","family":"Larsen","sequence":"additional","affiliation":[{"name":"Emory Transplant Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy L","family":"Ford","sequence":"additional","affiliation":[{"name":"Emory Transplant Center , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"2025030702143860800_r1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech","year":"2012","journal-title":"Nat. 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