Date: Saturday, May 30, 2020
Session Name: Poster Session C: Immunosuppression Preclinical Studies
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: In humans, CD4+CD45RA–Foxp3hi T cells comprise a regulatory T cell (Treg) subset with highly suppressive function. We have previously shown that granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) administration enhances the incidence of peripheral blood CD4+CD25hiFoxp3hi Treg in non-human primates. Here, we examined whether GM-CSF/G-CSF administration enhances the incidence of CD4+CD45RA–Foxp3hi Treg in leukapheresis products (LP) of rhesus monkeys.
*Methods: Rhesus monkeys (n=6; 5-7kg) were treated sequentially with recombinant human GM-CSF (10 mg/kg/day for 4 days), then recombinant human G-CSF (10 mg/kg/day for 4 days), followed by leukapheresis. Treg in peripheral blood mononuclear cells (PBMC), obtained before treatment, and in LP obtained after GM-CSF/G-CSF administration were assessed based on their expression of CD45RA, CD25 and Foxp3. The percentages and phenotype of CD4+CD45RA–Foxp3hi Treg and CD4+CD45RA–Foxp3lo populations were evaluated. Additionally, LP CD4+CD45RA–CD25lo and CD4+CD45RA–CD25hi populations were flow-sorted and assessed for their suppressive function.
*Results: After G-CSF/GM-CSF administration, the incidence of CD4+CD45RA–Foxp3hi Treg increased significantly in LP (p<0.01), compared to peripheral blood before treatment. Furthermore, the ratio of CD4+CD45RA–Foxp3hi to CD4+CD45RA–Foxp3lo cells also increased significantly (p<0.05). In LP, The CD4+CD45RA–CD25hi population expressed significantly higher levels of Foxp3, CTLA4 and Helios, compared to the CD4+CD45RA–CD25lo population (p<0.05). In 3 animals, LP flow-sorted CD4+CD45RA–CD25hi cells exhibited superior suppression of T cell proliferation in response to anti-CD2/CD3/CD28 stimulation, compared to the CD4+CD45RA–CD25hi population.
*Conclusions: G-CSF/GM-CSF administration enhances the incidences of highly suppressive CD4+CD45RA–Foxp3hi T cells in LP of mobilized rhesus monkeys. These observations further support the therapeutic potential of Treg-enriched LP from mobilized individuals.
To cite this abstract in AMA style:Sasaki K, Wang Y, Lu L, Hughes J, Vujevich V, Thomson AW, Ezzelarab MB. Granulocyte-Colony Stimulating Factor (G-CSF) and Granulocyte-Macrophage CSF (GM-CSF) Administration Enriches for Highly Suppressive CD4+CD45RA–Foxp3hi Cells in Leukapheresis Products of Rhesus Monkeys [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/granulocyte-colony-stimulating-factor-g-csf-and-granulocyte-macrophage-csf-gm-csf-administration-enriches-for-highly-suppressive-cd4cd45ra-foxp3hi-cells-in-leukapheresis-products-of-rhesus-monkey/. Accessed March 6, 2021.
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