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

Background Our laboratory previously reported that leukemia patients who developed greater than or equal to 10% gamma delta(+) T cells during the first six-months after receiving an anti-TCR alpha beta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gamma delta(+) T cells were V delta 1(+)CD3(+)CD4(-)CD8(-)CD69(+)HLADR(+) and are cytotoxic to K562 cells. Methods In order to determine wheather the anti-alpha beta TCD regimen was associated with these findings, we recieved TCD PMRD grafts using gamma delta(+) T cells from patients who recieved TCD PMRD grafts using the anti-TCR alpha beta MAb T10B9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3. Results Increased cytotoxic V delta 1(+) T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCP group (23% versus 7%, p = 0.010). T10B9 patients with incresed gamma delta(+) T cells also exhibited a higher range of increased gamma delta(+) T cells and the length of time the gamma delta(+) T cells remained high was longer when compared to OKT3 patients. Patients with increased gamma delta(+) T cells whose grafts were T-cell depleted with T-cell showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significant was not reached due to the small number of patients with increased gamma delta(+) T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gamma delta(+) T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091). Discussion These observations indicate that V delta 1(+)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.