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The Journal of Immunology, 2001, 166: 112-120.
Copyright © 2001 by The American Association of Immunologists

Cell Division Is Not a "Clock" Measuring Acquisition of Competence to Produce IFN-{gamma} or IL-4

Shlomo Z. Ben-Sasson*,{dagger}, Regina Gerstel*, Jane Hu-Li{dagger} and William E. Paul1,{dagger}

* Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel; and {dagger} Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Naive CD4 T cells acquire the potential to produce IFN-{gamma} and IL-4 by culture in the presence of their cognate Ag, APC, and appropriate cytokines. In this study, we show that commitment to IFN-{gamma} production on the part of rigorously purified naive CD4 T cells can occur without cell division. Indeed, even entry into S phase is not essential. Moreover, both CD4 and CD4/CD8 thymocytes from TCR-transgenic mice (5CC7 mice) on a Rag2-/- background can acquire IFN-{gamma}-producing capacity when stimulated by peptide, APC, and IL-12. These cells can do so without dividing and some acquire IFN-{gamma}-producing activity without entry into S phase. Not only is cell division not required for acquisition of cytokine-producing potential, cell populations that have undergone the same numbers of divisions can have quite different proportions of IFN-{gamma}- or IL-4-producing cells, depending on the duration of priming or, in the case of IL-4, on the concentration of peptide. Thus, cell division is not a clock for the expression of these cytokines. Factors associated with priming conditions including strength of stimulation, duration of priming, and number of divisions each play a role.




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