Figure 4. Adoptive cell therapy with alloprimed CXCR5⁺CD8⁺ T cells into CCR5 KO kidney transplant recipients significantly inhibits alloantibody production.

CCR5 KO (H-2^b) mice were transplanted with an allogeneic kidney (A/J, H-2^a). On day 5 posttransplant, a cohort of CCR5 KO recipients received adoptive cell therapy (ACT) with 0.5×10⁶, 1×10⁶, or 2×10⁶ flow-sorted alloprimed CXCR5⁺CD8⁺ T cells (retrieved from A/J allolysate primed C57BL/6, H-2^b, mice). Day 14 posttransplant serum from kidney transplant recipients was analyzed for alloantibody titer. Alloantibody production was significantly reduced following ACT with 1×10⁶ CXCR5⁺CD8⁺ T cells (titer = 2,800±1,100, n=4; *p=0.0015) and ACT with 2×10⁶ cells (titer = 1,300±240, n=9; **p<0.0001) compared to CCR5 KO recipients without ACT (titer= 6,000±630, n=7). Both ACT of 1×10⁶ and 2×10⁶ alloprimed CXCR5⁺CD8⁺ T cells inhibited alloantibody titer more than ACT with 0.5×10⁶ alloprimed cells (^†p<0.0002 for both). No significant reduction was observed with ACT with 0.5×10⁶ alloprimed CXCR5⁺CD8⁺ T cells (titer = 7,300±700, n=4), 2×10⁶ 3^rd party primed (FVB/N, H-2^q) CXCR5⁺CD8⁺ T cells (titer = 5,100±370, n=5), or with 2×10⁶ alloprimed CXCR5⁻CD8⁺ T cells (titer= 5,100±470, n=5). Recipient mice that received ACT with either 2×10⁶ 3^rd party primed CXCR5⁺CD8⁺ T cells or alloprimed CXCR5⁻CD8⁺ T cells had significantly higher alloantibody titers compared to recipients that received 2×10⁶ alloprimed CXCR5⁺CD8⁺ T cells (^‡p<0.0001 for both). Dashed line represents naïve control sera.