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- W4313405873 abstract "Abstract Kidney transplant (KTx) into CCR5 KO mice is an excellent model to study AMR immunobiology due to a heightened humoral response posited to be secondary to impaired CD4+Treg cell trafficking to the allograft. We have observed that adoptive cell therapy (ACT) with alloprimed CXCR5+CD8+ T cells mediates significant reduction of alloAb titer in CCR5 KO KTx recipients. We hypothesized that CXCR5+CD8+ T cells are more potent inhibitors of alloAb production than CD4+Tregs. We found that CCR5 KO recipients have significantly fewer CXCR5+CD8+ T cells (782±183 vs 2058±167 cells/mm3) and graft-infiltrating CD4+Treg cells (CD25+FoxP3+; 12.9±8.8 vs 56.2±8.8 cells/mm3) compared to WT recipients, as well as significantly greater quantity of splenic germinal center (GC; GL7+Fas+B220+) B cells (5814±436 vs 671±342 cells/mm3; all p<0.003). CCR5 KO recipient alloAb titer is significantly reduced following CXCR5+CD8+ T cell ACT (1259±436 vs 5951±404 in untreated controls; p<0.0001) but not following CD4+Treg ACT (5688±436). CXCR5+CD8+ T cells reduced splenic GC B cell (5813±589 to 4087±537; p=0.002) quantity, while CD4+Treg had no impact (6916±538/mm3). Compared to untreated controls, CD8-depletion in WT recipients led to significant increase in alloAb titer (1508±338 vs 6078±436) and GC B cells (671±436 vs 7761±430; p<0.0001 for both). CD4+Treg depletion led to increased alloAb titer (3180±436) and GC B cell quantity (4911±429; p<0.004 for both), though less pronounced than in the CD8-depleted group (both p<0.001). This suggests that CXCR5+CD8+ T cells are more potent regulators of alloAb production than CD4+Tregs and their deficiency in CCR5 KO recipients is the major driver of heightened humoral immunity and AMR following KTx. Supported by NIH R01 AI083456 (to GLB), T32 AI106704-07 and F32 AI161844 (to JLH), CA016058, UL1TR002733, the OSU Division of Transplant Surgery, and the OSU College of Medicine." @default.
- W4313405873 created "2023-01-06" @default.
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- W4313405873 date "2022-05-01" @default.
- W4313405873 modified "2023-10-14" @default.
- W4313405873 title "Deficiency of antibody-suppressor CXCR5+CD8+ T cells (not CD4+ Tregs) drives high alloantibody production in CCR5 KO kidney transplant recipients" @default.
- W4313405873 doi "https://doi.org/10.4049/jimmunol.208.supp.175.09" @default.
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