Influence of T cell depletion method on circulating γδ T cell reconstitution and potential role in the graft-versus-leukemia effect

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Abstract
Our laboratory previously reported that leukemia patients who developed ≥ 10% γδ+ T cells during the first six months after receiving an anti-TCRαβ T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These γδ+ T cells were Vδ1+CD3+ CD4−CD8−CD69+HLADR+ and are cytotoxic to K562 cells. In order to determine whether the anti-αβ TCD regimen was associated with these findings, we compared the reconstitution of γδ+ T cells from patients who received TCD PMRD grafts using the anti-TCRαβ MAb T10B9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3. Increased cytotoxic Vδ1+ T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCD group (23% versus 7%, p = 0.010). T10B9 patients with increased γδ+ T cells also exhibited a higher range of increased γδ+ T cells and the length of time the γδ+ T cells remained high was longer when compared to OKT3 patients. Patients with increased γδ+ T cells whose grafts were T-cell depleted with T10B9 showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significance was not reached due to the small number of patients with increased γδ+ T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased γδ+ T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091). These observations indicate that Vδ1+CD4−CD8−cytotoxic T cells are associated with lower relapse rates and improved survival, and thus may have a role in a graft-versus-leukemia effect.

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