Influence of T cell depletion method on circulating gammadelta T cell reconstitution and potential role in the graft-versus-leukemia effect.
BACKGROUND
Our laboratory previously reported that leukemia patients who developed > or = 10% gammadelta+ T cells during the first six months after receiving an anti-TCRalphabeta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gammadelta+ T cells were V81+CD3+CD4-CD8-CD69+HLADR+ and are cytotoxic to K562 cells.


METHODS
In order to determine whether the anti-alphabeta TCD regimen was associated with these findings, we compared the reconstitution of gammadelta+ T cells from patients who received TCD PMRD grafts using the anti-TCRc4 MAb TIOB9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3.


RESULTS
Increased cytotoxic Vdelta1+ 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 gammadelta+ T cells also exhibited a higher range of increased gammadelta+ T cells and the length of time the gammadelta+ T cells remained high was longer when compared to OKT3 patients. Patients with increased gammadelta+ 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 gammadelta+ T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gammadelta+ T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091).


CONCLUSIONS
These observations indicate that Vdelta1+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.
Lamb
L S
LS
Division of Transplantation Medicine, Palmetto Richland Memorial Hospital, Center for Cancer Treatment and Research, University of South Carolina School of Medicine, Columbia, South Carolina 29203, USA.
Gee
A P
AP
Hazlett
L J
LJ
Musk
P
P
Parrish
R S
RS
O'Hanlon
T P
TP
Geier
S S
SS
Folk
R S
RS
Harris
W G
WG
McPherson
K
K
Lee
C
C
Henslee-Downey
P J
PJ
D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion / Q000379:methods; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007223:Infant; D020014:K562 Cells; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
D016692:Receptors, Antigen, T-Cell, gamma-delta