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Immunology Research Division, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
To examine the functional characteristics of memory
CD4+ T cells, we used an adoptive transfer system to
generate a stable population of Ag-specific memory cells in vivo and
compared their responses to Ag with those of a similar population of
Ag-specific naive cells. Memory cells localized to the spleen and lymph
nodes of mice and exhibited extremely rapid recall responses to Ag in
vivo, leaving the spleen within 3–5 days of Ag encounter. Unlike their
naive counterparts, memory cells produced effector cytokines (IFN-
,
IL-4, IL-5) within 12–24 h of Ag exposure and did not require multiple
cycles of cell division to do so. Memory cells proliferated at lower Ag
concentrations than did naive cells, were less dependent on
costimulation by B7 molecules, and independent of costimulation by
CD40. Furthermore, effector cytokine production by memory cells also
occurred in the absence of either B7 or CD40 costimulation. Lastly,
memory cells were resistant to tolerance induction. Together, these
findings suggest that the threshold for activation of memory
CD4+ cells is lower than that of naive cells. This would
permit memory cells to rapidly express their effector functions in vivo
earlier in the course of a secondary immune response, when the levels
of Ag and the availability of costimulation may be relatively
low.
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 N. Hayashi, D. Liu, B. Min, S. Z. Ben-Sasson, and W. E. Paul Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells PNAS, April 30, 2002; 99(9): 6187 - 6191. [Abstract] [Full Text] [PDF]
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H. Gudmundsdottir and L. A. Turka A Closer Look at Homeostatic Proliferation of CD4+ T Cells: Costimulatory Requirements and Role in Memory Formation J. Immunol., October 1, 2001; 167(7): 3699 - 3707. [Abstract] [Full Text] [PDF]
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S. Mirshahidi, C.-T. Huang, and S. Sadegh-Nasseri Anergy in Peripheral Memory CD4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor J. Exp. Med., September 10, 2001; 194(6): 719 - 732. [Abstract] [Full Text] [PDF]
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M. Ahmadzadeh, S. F. Hussain, and D. L. Farber Heterogeneity of the Memory CD4 T Cell Response: Persisting Effectors and Resting Memory T Cells J. Immunol., January 15, 2001; 166(2): 926 - 935. [Abstract] [Full Text] [PDF]
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Z.-Q. Wu, A. Q. Khan, Y. Shen, J. Schartman, R. Peach, A. Lees, J. J. Mond, W. C. Gause, and C. M. Snapper B7 Requirements for Primary and Secondary Protein- and Polysaccharide-Specific Ig Isotype Responses to Streptococcus pneumoniae J. Immunol., December 15, 2000; 165(12): 6840 - 6848. [Abstract] [Full Text] [PDF]
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N. Hayashi, D. Liu, B. Min, S. Z. Ben-Sasson, and W. E. Paul Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells PNAS, April 30, 2002; 99(9): 6187 - 6191. [Abstract] [Full Text] [PDF]
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