Effector CD8+ T cells activated in vitro confer immediate and long-term tumor protection in vivo.
We studied the ability of CD8+ T cells activated in vitro to mediate tumor protection after transfer into adoptive hosts. TCR transgenic CD8+ T cells were activated in culture with DC and specific peptide antigen, and briefly expanded in IL-2 containing medium. Cultured cells acquired a CD44hiCD62Llo phenotype, and following in vivo transfer they preferentially homed to non-lymphoid tissues and spleen. In vivo, their numbers declined between day 0 and day 20, and then remained relatively stable from day 20 to day 90. Over time, many of the injected cells re-expressed CD62L, and acquired the ability to localize to secondary lymphoid organs. Transferred T cells underwent low-level proliferation, expressed IL-7Ralpha and IL-15Rbeta, were cytotoxic in vivo, and retained the ability to produce IL-2, IFN-gamma and TNF-alpha upon ex vivo restimulation. In addition, transferred T cells conferred a high degree of tumor protection, which was greatest immediately after injection, and remained significant even when tumor was given 90 days after T-cell transfer. We conclude that in vitro generated effector T cells can mediate immediate and long-term tumor protection, and develop into long-lived memory T-cell populations in vivo.
Perret
Rachel
R
Malaghan Institute of Medical Research, Wellington, New Zealand.
Ronchese
Franca
F
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
C508022:Il2rb protein, mouse; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D020395:Receptors, Interleukin-7; D014409:Tumor Necrosis Factor-alpha; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma