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bioRxiv · 10.1101/2022.01.11.475845

Differentiation of a CD4+/CD8αβ+ Double Positive T Cell Population From The CD8 Pool Is Sufficient To Mediate Graft-vs-Host Disease but not Graft-vs-Leukemia Effects

Hess, N. J.·Turicek, D. P.·Nadiminti, K.·Hudson, A.·Hematti, P.·Gumperz, J. E.·Capitini, C. M.
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Abstract

An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-vs-host disease (GVHD) while preserving the graft-vs-leukemia (GVL) activity of donor T cells. From an observational clinical study of adult allo-HCT recipients, we identified a CD4+/CD8+ double positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of [≥] grade 2 GVHD. Using an established xenogeneic transplant model, we reveal that the DPT population develop from antigen stimulated CD8 T cells which become transcriptionally, metabolically and phenotypically distinct from single-positive CD4 and CD8 T cells. Isolated DPTs were sufficient to mediate xeno-GVHD pathology when re-transplanted into naive mice but provided no survival benefit when mice were challenged with a human B-ALL cell line. Overall, this study reveals human DPTs as a T cell population directly involved with GVHD pathology. One Sentence SummaryHuman CD4+/CD8+ double positive T cells (DPTs) mediate xenogeneic GVHD but possess limited GVL activity.

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Hess, N. J., Turicek, D. P., Nadiminti, K., Hudson, A., Hematti, P., Gumperz, J. E., Capitini, C. M.. 2022-01-12. Differentiation of a CD4+/CD8αβ+ Double Positive T Cell Population From The CD8 Pool Is Sufficient To Mediate Graft-vs-Host Disease but not Graft-vs-Leukemia Effects. https://doi.org/10.1101/2022.01.11.475845

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