Therapeutic efficacy of adoptive immunotherapy is predicated on in vivo antigen-specific proliferation of donor T cells

Clin Immunol. 2003 Jul;108(1):8-20. doi: 10.1016/s1521-6616(03)00090-1.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation
  • Cell Division / immunology*
  • Cell Division / radiation effects
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Predictive Value of Tests
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / radiation effects
  • Whole-Body Irradiation