Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Memory T cells primed with microbial antigen can cross-react with alloantigen and mediate graft rejection, a process termed allogeneic heterologous immunity. Human and murine studies have shown that a significant portion of pathogen-specific memory T cells can be alloreactive, and it is assumed that these cells drive heterologous graft rejection. CD45 is a transmembrane phosphatase that plays an important role in tuning T cell receptor (TCR) signaling and is regarded as a T cell differentiation marker. Naive peripheral T cells have high CD45RB isoform expression (denoted CD45RBhi) while effector and memory CD8+ T cells are described as having low expression of the CD45RB isoform (CD45RBlo). In this study, we sought to interrogate the role of CD45RB on memory CD8+ T cells during heterologous immunity.
*Methods: We assessed the phenotype and function of CD44hi and tetramer+ CD8+ T cells following acute LCMV Armstrong infection at memory timepoints and following H-2d Balb/c skin graft rechallenge of LCMV infected mice.
*Results: We found that following acutely cleared viral infection with LCMV, the viral-specific memory CD8+T cell population surprisingly included approximately equal populations of CD45RBhi and CD45RBlo cells. A 2D micropipette affinity assay revealed that CD45RBhi memory cells had a 29-fold lower affinity for antigen relative to CD45RBlo cells. CD45RBlo and CD45RBhi memory cells expressed similar levels of granzyme B and IFN-γ, but RNASeq analysis revealed that these populations differentially expressed over 150 genes. Phenotypically, the CD45RBhi population contained a higher frequency of the CD62LhiCD27hiCD127hiKLRG1lo persistent memory phenotype compared to CD45RBlo cells. We found that from early to late memory time-points, portions of each of the CD45RBhi and CD45RBlo populations underwent conversion to CD62Lhi, demonstrating that CD45RB status is distinct from the TCM phenotype. Adoptive transfer of purified CD45RBhi and CD45RBlo populations into naïve mice revealed that CD45RBlo memory cells underwent significant cell loss relative to CD45RBhi memory cells. Over time, the majority of CD45RBlo cells homeostatically converted to the CD45RBhi persistent memory phenotype. Finally, following fully mismatched allogeneic skin graft in LCMV immune mice, approximately 80% of donor-specific memory CD8+T cells remained CD45RBhi.
*Conclusions: Together, these data demonstrate a that CD45RB status correlates with memory persistence, which has implications for the therapeutic strategies aimed at eliminating heterologous immune responses.
To cite this abstract in AMA style:Krummey SM, Morris AB, Ford ML. Cd45rb Mediates Cd8+T Cell Persistence In An Allogeneic Heterologous Immune Response [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/cd45rb-mediates-cd8t-cell-persistence-in-an-allogeneic-heterologous-immune-response/. Accessed March 8, 2021.
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