TY - JOUR
T1 - Characterization of circulating and cultured Tfh-like cells in sickle cell disease in relation to red blood cell alloimmunization status
AU - Balbuena-Merle, Raisa
AU - Santhanakrishnan, Manjula
AU - Devine, Lesley
AU - Gibb, David R.
AU - Tormey, Christopher A.
AU - Siddon, Alexa J.
AU - Curtis, Susanna A.
AU - Gallagher, Patrick G.
AU - Weinstein, Jason S.
AU - Hendrickson, Jeanne E.
N1 - Funding Information: This work was supported in part by the National Institutes of Health [ R01 HL132951 (to JEH), T32 HL007974-14 (to Brian Smith, for RBM and SAC), K08 HL141446 (to DRG), and 5R01 AR068994 (to Joseph Craft and PGG)]. This work was also supported in part by the National Cancer Institute , [ P30CA016359 ]. Publisher Copyright: © 2020 Elsevier Ltd
PY - 2020/8
Y1 - 2020/8
N2 - Background: People living with sickle cell disease (SCD) are prone to red blood cell (RBC) alloimmunization. We hypothesized that subjects with alloantibodies (responders) would have differences in circulating T-follicular helper (Tfh)-like cells compared to subjects without alloantibodies (non-responders). Materials and methods: Peripheral blood mononuclear cells were collected from 28 subjects, including those with SCD and controls. Circulating CD4 T-cell subsets were first evaluated at baseline. CD4 T-cell subsets were also evaluated after naïve CD4 T-cells were differentiated into Tfh-like cells following in vitro culture with CD3/CD28 beads, IL-7, IL-12, and Activin A. Transfusion and alloantibody histories were extracted from the electronic medical record. Results: Non-responders had a lower percentage of CD45RA negative Tmemory cells than responders or controls (p<0.05). Notably, there were no differences in circulating Tfh-like cells between any group. However, naïve CD4 T-cells from subjects with SCD were more likely to express CXCR5 after in vitro culture than cells from controls. After culture, CXCR5 expressing cells from responders were more likely to express PD1 and ICOS (16.43 %, sd. 20.23) compared to non-responders (3.69 %, s.d. 3.09) or controls (2.78 %, s.d. 2.04). Discussion: The tendency for naïve CD4 T-cells from responders to differentiate into Tfh-like cells after in vitro culture may suggest these cells are prepared to assist B-cells with antibody production regardless of antigen specificity. Further studies are needed, but it is possible that these results may explain why some responders form RBC alloantibodies with multiple specificities, in addition to RBC autoantibodies and HLA alloantibodies.
AB - Background: People living with sickle cell disease (SCD) are prone to red blood cell (RBC) alloimmunization. We hypothesized that subjects with alloantibodies (responders) would have differences in circulating T-follicular helper (Tfh)-like cells compared to subjects without alloantibodies (non-responders). Materials and methods: Peripheral blood mononuclear cells were collected from 28 subjects, including those with SCD and controls. Circulating CD4 T-cell subsets were first evaluated at baseline. CD4 T-cell subsets were also evaluated after naïve CD4 T-cells were differentiated into Tfh-like cells following in vitro culture with CD3/CD28 beads, IL-7, IL-12, and Activin A. Transfusion and alloantibody histories were extracted from the electronic medical record. Results: Non-responders had a lower percentage of CD45RA negative Tmemory cells than responders or controls (p<0.05). Notably, there were no differences in circulating Tfh-like cells between any group. However, naïve CD4 T-cells from subjects with SCD were more likely to express CXCR5 after in vitro culture than cells from controls. After culture, CXCR5 expressing cells from responders were more likely to express PD1 and ICOS (16.43 %, sd. 20.23) compared to non-responders (3.69 %, s.d. 3.09) or controls (2.78 %, s.d. 2.04). Discussion: The tendency for naïve CD4 T-cells from responders to differentiate into Tfh-like cells after in vitro culture may suggest these cells are prepared to assist B-cells with antibody production regardless of antigen specificity. Further studies are needed, but it is possible that these results may explain why some responders form RBC alloantibodies with multiple specificities, in addition to RBC autoantibodies and HLA alloantibodies.
KW - Red blood cell alloimmunization
KW - Sickle cell disease
KW - Tfh-like cells
KW - Transfusion medicine
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U2 - https://doi.org/10.1016/j.transci.2020.102778
DO - https://doi.org/10.1016/j.transci.2020.102778
M3 - Article
C2 - 32439490
SN - 1473-0502
VL - 59
JO - Transfusion and Apheresis Science
JF - Transfusion and Apheresis Science
IS - 4
M1 - 102778
ER -