Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
CD8+ memory T cells produce IFN-g in a faster and stronger fashion than their naïve counterparts after allorecognition. Unmanipulated mice possess a proportion of endogenous memory T cells that contain an alloreactive population. The contribution of such endogenous alloreactive memory T cells in allograft rejection is still unclear. In this study we investigated the ability of endogenous memory cells and bona fide memory T cells induced after allosensitization to produce IFN-y after stimulation in vitro with allogeneic stimulators (direct allorecognition).
BALB/c mice (H2kd) were sensitized with a fully MHC mismatched C57BL/6 (H-2b) skin graft and splenocytes were isolated after 7-10 days (early sensitized) or 40-60 days (late sensitized) and compared with age-matched recipients of a syngeneic graft and unmanipulated controls. IFN-y production was assessed using ELISPOT and flow cytometry after stimulation with donor stimulators (direct allorecognition).
Splenocytes from a late sensitized mouse showed IFN-y production by ELISPOT as soon as 2 hours after allo stimulation (x̅ = 121 spots/million responders SD 26.3), whereas splenocytes from an early sensitized mouse and an unmanipulated mouse could only produce a response after 4 and 24 hours stimulation, respectively (x̅=53 spots/million responders SD 50.5; x̅= 43.8 spots/million responders SD 10.9). Furthermore, after 4 hours direct TCR stimulation through anti-CD3/CD28 mAb-coated beads, IFN-y production was lower in the unmanipulated group compared to the late sensitized one (p<0.001).
IFN-y producing cells were detected through flow cytometry primarily in the CD3+ CD8+CD44highCD69+ T cell compartment. 1.89% of the cells with this phenotype produced IFN-y in an unmanipulated mouse, in contrast with 17.2% in the late sensitized mouse (p<0.0001) after a 4 hour mixed lymphocyte reaction with the alloantigen.
Alloreactive endogenous memory T cells are not capable of producing IFN-y in the same fashion as allotransplant-induced memory T cells in our model.
CITATION INFORMATION: Gonzalez-Nolasco B, Marino J, Orent W, Benichou G. Differences in Kinetics of IFN-y Production Between Endogenous and Allotransplant-Induced Memory T Cells. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Gonzalez-Nolasco B, Marino J, Orent W, Benichou G. Differences in Kinetics of IFN-y Production Between Endogenous and Allotransplant-Induced Memory T Cells. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/differences-in-kinetics-of-ifn-y-production-between-endogenous-and-allotransplant-induced-memory-t-cells/. Accessed December 12, 2019.
« Back to 2017 American Transplant Congress