Suppressor function of lymphocytes activated in in vitro co-culture against autologous tumor cells and expanded in interleukin-2.
The phenotypic and functional nature of the lymphocytes that have been activated against autologous tumor cells and expanded in Interleukin-2 (IL-2) was studied in the context of their suitability for use in adoptive immunotherapy for cancer. While long-term co-cultures between autologous lymphocytes and tumor cells in the presence of exogenous IL-2 occasionally induced CD8+ cytolytic T cells, a substantial majority of such co-cultures generated predominantly CD4+ non-cytolytic or poorly cytolytic effector cells. In addition, these CD4+ non-cytolytic effector populations, and a number of CD4+ T cell clones derived from them, behaved like functional T suppressor (Ts) cells by elaborating a factor(s) that had profound negative effect(s) on activation of fresh T cells (inhibition of IL-2 synthesis, inhibition of IL-2 receptor [IL-2]-alpha expression, and inhibition of proliferation). Accordingly, infusion of these non-cytolytic populations capable of exhibiting such regulatory properties may have a substantial negative effect on host response toward cancer.
Okino
T
T
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030.
Chakraborty
N G
NG
Ergin
M T
MT
Mukherji
B
B
D001681:Biological Assay; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015375:Receptors, Interleukin-2