Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leukocyte cultures.

Details

Serval ID
serval:BIB_994194CA3C84
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leukocyte cultures.
Journal
The Journal of experimental medicine
Author(s)
Macdonald H.R., Engers H.D., Cerottini J.C., Brunner K.T.
ISSN
0022-1007
ISSN-L
0022-1007
Publication state
Published
Issued date
01/09/1974
Peer-reviewed
Oui
Volume
140
Number
3
Pages
718-730
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Mouse cytotoxic T lymphocytes (CTL) were generated in unidirectional mixed leukocyte cultures (MLC) using normal C57BL/6 spleen cells as responding cells and irradiated DBA/2 spleen cells as stimulating cells. Cytotoxicity was assayed on (51)Cr-labeled P-815 (DBA/2) target cells, and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Upon inclusion of 2-mercaptoethanol in the culture medium, it was found that significant CTL activity could be detected for as long as 3 wk in primary MLC. Reexposure of MLC cells to the original stimulating alloantigens after 14-41 days in culture resulted in significant cell proliferation and rapid regeneration of high levels of immunologically specific cytotoxicity. CTL activity in these secondary cultures increased dramatically within the first 24 h and reached higher peak levels than those found at the peak of the primary response. Furthermore, proliferation and reappearance of CTL activity could be demonstrated following each of as many as four sequential alloantigenic stimulations of the same initial cell population at 20-day intervals. Interestingly, cells recovered from MLC at the peak of the primary response on day 4 were insensitive to further allogeneic stimulation. Taken together, these results are consistent with the hypothesis that CTL differentiate in MLC to become long-lived memory cells which gradually lose their cytotoxic activity. Upon reexposure to specific alloantigen, such memory CTL rapidly regain their functional activity and proliferate to generate an expanded CTL population.
Keywords
Animals, Antigen-Antibody Reactions/drug effects, Antigen-Antibody Reactions/radiation effects, Cell Division, Cell Survival, Cells, Cultured, Chromium Radioisotopes, Cytotoxicity Tests, Immunologic, Female, Immunity, Cellular, Immunologic Memory, Isoantigens, Kinetics, Lymphocyte Culture Test, Mixed, Mercaptoethanol/pharmacology, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Spleen/cytology, Spleen/immunology, T-Lymphocytes/cytology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, T-Lymphocytes/radiation effects
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:14
Last modification date
13/07/2024 7:09
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