TY - JOUR
T1 - Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells
AU - Hayashi, Nobuki
AU - Liu, Dacai
AU - Min, Booki
AU - Ben-Sasson, Shlomo Z.
AU - Paul, William E.
PY - 2002/4/30
Y1 - 2002/4/30
N2 - TH1 memory T cells derived from T cell receptor transgenic mice, in which the T cell antigen receptor is specific for a cytochrome C peptide in association with I-Ek, were transferred into normal B10.A mice and allowed to adopt a resting phenotype. When challenged, 30-60 days after transfer, with i.v. cytochrome C, the transgenic cells rapidly became activated, expressed mRNA for IFNγ, and began to divide. However, after 48 h, the frequency of the cells fell progressively, reaching levels only slightly above the limit of detection by day 8 and thereafter remain depressed for up to 90 days. The remaining cells were anergic as shown by limitation in proliferation and IFNγ production in response to in vitro antigen stimulation. Even if challenged with antigen emulsified in complete Freund's adjuvant, the overall pattern was similar, except that in the draining lymph nodes, the surviving antigen-specific cells were not anergic, although spleen cells were still strikingly anergic. Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory.
AB - TH1 memory T cells derived from T cell receptor transgenic mice, in which the T cell antigen receptor is specific for a cytochrome C peptide in association with I-Ek, were transferred into normal B10.A mice and allowed to adopt a resting phenotype. When challenged, 30-60 days after transfer, with i.v. cytochrome C, the transgenic cells rapidly became activated, expressed mRNA for IFNγ, and began to divide. However, after 48 h, the frequency of the cells fell progressively, reaching levels only slightly above the limit of detection by day 8 and thereafter remain depressed for up to 90 days. The remaining cells were anergic as shown by limitation in proliferation and IFNγ production in response to in vitro antigen stimulation. Even if challenged with antigen emulsified in complete Freund's adjuvant, the overall pattern was similar, except that in the draining lymph nodes, the surviving antigen-specific cells were not anergic, although spleen cells were still strikingly anergic. Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory.
KW - Anergy
KW - Apoptosis
KW - Immunologic memory
KW - TH1 cells
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0037197917&partnerID=8YFLogxK
U2 - 10.1073/pnas.092129899
DO - 10.1073/pnas.092129899
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C2 - 11959916
AN - SCOPUS:0037197917
SN - 0027-8424
VL - 99
SP - 6187
EP - 6191
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 9
ER -