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

Background Our laboratory previously reported that leukemia patients who developed gre ater than or equal to 10% gamma delta(+) T cells during the first six-month s 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 associat ed 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 b eta 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 pa tients 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 hig her range of increased gamma delta(+) T cells and the length of time the ga mma delta(+) T cells remained high was longer when compared to OKT3 patient s. 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, alth ough significant was not reached due to the small number of patients with i ncreased gamma delta(+) T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gamma delta(+) T c ells (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.