*Purpose: It is well known that CD4⁺ T cells provide “help” for antibody production in vivo. Our group discovered a novel subset of murine antibody-suppressor CD8⁺ T cells which significantly downregulates alloantibody production in murine models of hepatocyte, islet, skin and kidney transplant. The current study aimed to prospectively investigate the correlation of peripheral blood CD8⁺ and CD4⁺ T cell subsets in humans with the development of de novo donor specific antibody (DSA) after kidney transplantation (Tx).

*Methods: We prospectively and serially (pre-Tx,1, 3, 6, 9 and 12 months postTx) analyzed peripheral blood mononuclear cells (PBMC) by flow cytometry and monitored for the development of de novo DSA during the first year postTx. We report results on 95 first-time human kidney Tx recipients (53.3±11.8 years old, 41% female, 21% African American) with one-year follow-up (19.7±2.9 months follow-up). All recipients received the same induction and maintenance immunosuppression.

*Results: Twenty-three (24.2%) developed de novo DSA within 1-year postTx (first detected an average 6.0±3.7 months postTx). CD8⁺ T cells expressing the same phenotype as murine antibody-suppressor CD8⁺ T cells were detected in all kidney Tx recipients; however, the quantity of this subset was significantly lower (2-fold) in DSA positive compared to DSA-negative recipients (4,400±600 vs. 8,200±900 cells per 10⁶ PBMC; p=0.02). In addition, the ratio of CD8⁺ T cells expressing the phenotype of murine antibody-suppressor CD8⁺ T cells to combined quantity of IFNγ⁺CD4⁺ Th1 and IL-4⁺ Th2 cells was significantly lower (2.5-fold) in DSA-positive compared to DSA-negative recipients(0.3±0.04 vs. 0.8±0.1; p=0.01). The development of DSA could not be attributed to differences in immunosuppression [both groups achieved similar target levels of CNi (760±42 ng/mL) and mTORi (7.5±0.3 ng/mL) throughout the first year postTx (p=ns)]. However, the DSA-positive group had a significantly higher rate of acute rejection (7/23, p=0.001) and trended towards greater graft loss (2/23, p=0.056) than the DSA-negative group (3/72 with rejection, 0/72 with graft loss) at 1-year postTx.

*Conclusions: These data suggest that monitoring of immune T cell subset quantity and ratios (pre- and/or post-Tx) may serve as a biomarker for assessing risk of developing de novo DSA. Furthermore, our results support the premise that a human correlate for murine antibody-suppressor CD8⁺ T cells exists in kidney Tx recipients.

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