The Property of Modulatory T Cells Generated by Mixed Lymphocyte Culture with CD154 Blockade.
Center for Transplantation Science, Massachusetts General Hospital, Boston, MA.
Meeting: 2016 American Transplant Congress
Abstract number: A27
Keywords: Alloantigens, CD4, Co-stimulation, T helper cells
Session Information
Session Type: Poster Session
Date: Saturday, June 11, 2016
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
Background:Regulatory T cell (Treg) immunotherapy has been applied to minimize the immunosuppressive drugs in clinical transplantation. To avoid contamination of CD4+CD25- T cells, only highly purified Tregs have been infused to the patients. In this study, we investigated immunological properties of CD4+CD25- T cells after mixed lymphocyte culture (MLC) with a costimulatory blockade.
Method: Isolated CD4+ T cells (Responder A) from human blood buffy coat were cultured with irradiated allogeneic PBMCs (Stimulator B) for 14 days in the presence or absence of anti-human CD154 mAb. These primed CD4+ T cells were then added as a modulator (Modulator A) to a newly prepared (second) MLC with Responder A and irradiated original stimulator (Simulator B) or third party stimulator (Stimulator C) for 5 days.
Results: There was no significant difference in the percentage of Tregs induced after MLC with or without aCD154mAb. However, Modulator A generated after MLC with aCD154mAb significantly more suppressed the second MLC than Modulator A generated without aCD154mAb. These modulators generated with aCD154mAb also displayed antigen-specific suppression as Modulator A generated by Stimulator B with anti-CD154 mAb in the first MLC significantly more suppressed the second MLC with Stimulator B than with Stimulator C (Fig. 1). To identify which T cell subset possesses suppressive function, CD4+CD25highFoxP3+ cells (Treg) and CD4+CD25-FoxP3- cells (non-Treg) were sorted after the first MLC. Treg isolated after the first MLC displayed significant suppressive function of the second MLC. Interestingly, although suppressive function was not prominent as Treg, non-Treg isolated after the first MLC also displayed suppressive function (Fig. 2).
Conclusion: These data indicate that suppressive function can be expected even with antigen-primed non-Treg. In vivo studies to evaluate a suppressive function of these non-Tregs are currently underway.
CITATION INFORMATION: Hotta K, Oura T, Cosimi B, Kawai T. The Property of Modulatory T Cells Generated by Mixed Lymphocyte Culture with CD154 Blockade. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Hotta K, Oura T, Cosimi B, Kawai T. The Property of Modulatory T Cells Generated by Mixed Lymphocyte Culture with CD154 Blockade. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/the-property-of-modulatory-t-cells-generated-by-mixed-lymphocyte-culture-with-cd154-blockade/. Accessed November 22, 2024.« Back to 2016 American Transplant Congress