Therapeutic efficacy of adoptive immunotherapy is predicated on in vivo antigen-specific proliferation of donor T cells.
Activated T cells with down-regulated L-selectin expression (L-sel(-)) from tumor-draining lymph nodes represent a potent source of specific immune effectors in adoptive immunotherapy. Using congenic pairs of mice and carboxyfluorescein diacetate succinimidyl ester-labeled L-sel(-) T cells, the current study analyzed in vivo proliferation of transferred cells. In the lung of MCA205 tumor-bearing mice, 6% or 0.3 x 10(6) of the 5 x 10(6) donor cells were identified 24 h after transfer. Vigorous proliferation of donor cells was evident on day 2, reaching a maximum on day 6. The proliferation was tumor-specific and CD4 T cells divided with greater magnitude than CD8 cells. Successful adoptive immunotherapy also required sublethal whole-body irradiation (WBI) of the recipient. WBI exerted its effects on facilitating specific T cell proliferation at the tumor site. Taken together, our results demonstrate that adoptively transferred T cells undergo extensive proliferation in response to the tumor and this response is associated with therapeutic efficacy.
Kjaergaard
Jørgen
J
Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Peng
Liaomin
L
Cohen
Peter A
PA
Shu
Suyu
S
D000818:Animals; D017951:Antigen Presentation; D002455:Cell Division / Q000276:immunology* / Q000528:radiation effects; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D014916:Whole-Body Irradiation