Donor T cells can be induced to grow and survive long term in vivo without previous host immunosuppression.
To examine whether donor T cells can grow and survive long term in hosts without previous immunosuppression, cultured T cells (B6/Thy 1.1) specific to FBL-3 tumor were adoptively transferred into normal B6/Thy 1.2 mice and induced to proliferate in vivo by specific stimulation with irradiated FBL-3. Donor T cells residing in the spleen and ascites of hosts were identified and quantified by use of Ab to the Thy-1 allele. The results demonstrated that on day 7 after transfer, donor T cells in greater numbers than input (1.2-fold) could be recovered. By day 35, donor T cells had decreased to approximately 10% of T cells input. Administration of IL-2 at doses of 2,500 or 25,000 U/day for 7 days preferentially increased the growth of Ag-activated donor T cells rather than host lymphocytes, and increased both the short term growth on day 7 (6.6-fold and 14.5-fold greater than input, respectively) and the long term survival on day 35 (0.75-fold and 3.15-fold of input, respectively) of donor T cells. The combination of CY pretreatment plus low dose IL-2 (2,500 U/day) increased donor T cell growth over and above that of either manipulation alone. However, with higher dose IL-2 to 25,000 U/day, donor T cell growth was equivalent in CY-pretreated and normal hosts (18-fold vs 16-fold increase, respectively; p > 0.05). With either dose of IL-2 there was no significant difference in the survival of donor T cells on day 35 in CY-pretreated vs normal hosts. Functional assay confirmed that specific cytolytic function of donor T cells could be maintained in hosts without previous immunosuppression. Accordingly, established disseminated FBL-3 leukemia could be cured without CY treatment, in a regimen using 10(7) cultured immune T cells plus IL-2 (25,000 U/day x 7 days). Thus, adoptively transferred donor T cells can be grown to large numbers and survive long term in vivo with maintenance of substantial function without the necessity of previous host immunosuppression.
Chen
W
W
Department of Medicine, University of Washington, Seattle 98195.
Cheever
M A
MA
D000818:Animals; D002470:Cell Survival; D003520:Cyclophosphamide / Q000494:pharmacology; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*
D007376:Interleukin-2; D003520:Cyclophosphamide