Naive CD8+ T cells differentiate into protective memory-like cells after IL-2 anti IL-2 complex treatment in vivo.
An optimal CD8(+) T cell response requires signals from the T cell receptor (TCR), co-stimulatory molecules, and cytokines. In most cases, the relative contribution of these signals to CD8(+) T cell proliferation, accumulation, effector function, and differentiation to memory is unknown. Recent work (Boyman, O., M. Kovar, M.P. Rubinstein, C.D. Surh, and J. Sprent. 2006. Science. 311:1924-1927; Kamimura, D., Y. Sawa, M. Sato, E. Agung, T. Hirano, and M. Murakami. 2006. J. Immunol. 177:306-314) has shown that anti-interleukin (IL) 2 monoclonal antibodies that are neutralizing in vitro enhance the potency of IL-2 in vivo. We investigated the role of IL-2 signals in driving CD8(+) T cell proliferation in the absence of TCR stimulation by foreign antigen. IL-2 signals induced rapid activation of signal transducer and activator of transcription 5 in all CD8(+) T cells, both naive and memory phenotype, and promoted the differentiation of naive CD8(+) T cells into effector cells. IL-2-anti-IL-2 complexes induced proliferation of naive CD8(+) T cells in an environment with limited access to self-major histocompatibility complex (MHC) and when competition for self-MHC ligands was severe. After transfer into wild-type animals, IL-2-activated CD8(+) T cells attained and maintained a central memory phenotype and protected against lethal bacterial infection. IL-2-anti-IL-2 complex-driven memory-like CD8(+) T cells had incomplete cellular fitness compared with antigen-driven memory cells regarding homeostatic turnover and cytokine production. These results suggest that intense IL-2 signals, with limited contribution from the TCR, program the differentiation of protective memory-like CD8(+) cells but are insufficient to guarantee overall cellular fitness.
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Daisuke
D
Kamimura
Michael J
MJ
Bevan
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism
D007376:Interleukin-2; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse