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Science 28 June 1996:
Vol. 272. no. 5270, pp. 1947 - 1950
DOI: 10.1126/science.272.5270.1947
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Reports

Induction of Bystander T Cell Proliferation by Viruses and Type I Interferon in Vivo

David F. Tough, Persephone Borrow, Jonathan Sprent *

T cell proliferation in vivo is presumed to reflect a T cell receptor (TCR)-mediated polyclonal response directed to various environmental antigens. However, the massive proliferation of T cells seen in viral infections is suggestive of a bystander reaction driven by cytokines instead of the TCR. In mice, T cell proliferation in viral infections preferentially affected the CD44hi subset of CD8+ cells and was mimicked by injection of polyinosinic-polycytidylic acid [poly(I:C)], an inducer of type I interferon (IFN I), and also by purified IFN I; such proliferation was not associated with up-regulation of CD69 or CD25 expression, which implies that TCR signaling was not involved. IFN I [poly(I:C)]-stimulated CD8+ cells survived for prolonged periods in vivo and displayed the same phenotype as did long-lived antigen-specific CD8+ cells. IFN I also potentiated the clonal expansion and survival of CD8+ cells responding to specific antigen. Production of IFN I may thus play an important role in the generation and maintenance of specific memory.

D. F. Tough and J. Sprent, Department of Immunology, IMM4, Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, USA.
P. Borrow, Department of Neuropharmacology, IMM6, Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, USA.
* To whom correspondence should be addressed.


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V. S. Cull, P. A. Tilbrook, E. J. Bartlett, N. L. Brekalo, and C. M. James (2003)
Blood 101, 2727-2735
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Type-I Interferon Receptor Deficiency Reduces Lupus-like Disease in NZB Mice.
M.-L. Santiago-Raber, R. Baccala, K. M. Haraldsson, D. Choubey, T. A. Stewart, D. H. Kono, and A. N. Theofilopoulos (2003)
J. Exp. Med. 197, 777-788
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Memory CD8+ T Cells Provide an Early Source of IFN-{gamma}.
T. Kambayashi, E. Assarsson, A. E. Lukacher, H.-G. Ljunggren, and P. E. Jensen (2003)
J. Immunol. 170, 2399-2408
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Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys.
S. Sopper, D. Nierwetberg, A. Halbach, U. Sauer, C. Scheller, C. Stahl-Hennig, K. Matz-Rensing, F. Schafer, T. Schneider, V. ter Meulen, et al. (2003)
Blood 101, 1213-1219
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Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections.
K. H. Ely, L. S. Cauley, A. D. Roberts, J. W. Brennan, T. Cookenham, and D. L. Woodland (2003)
J. Immunol. 170, 1423-1429
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Dialysis prior to li