Effector and Memory CD8+ T Cells Can Be Generated in Response to Alloantigen Independently of CD4+ T Cell Help

There is now considerable evidence suggesting that CD8(+) T cells are able to generate effector but not functional memory T cells following pathogenic infections in the absence of CD4(+) T cells. We show that following transplantation of allogeneic skin, in the absence of CD4(+) T cells, CD8(+) T ce...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2006-02, Vol.176 (4), p.2316-2323
Main Authors: Jones, Nick D, Carvalho-Gaspar, Manuela, Luo, Shiqiao, Brook, Matthew O, Martin, Laurent, Wood, Kathryn J
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell Proliferation
Cells, Cultured
Graft Rejection - immunology
Immunologic Memory - immunology
Interferon-gamma - metabolism
Isoantigens - immunology
Mice
Mice, Knockout
Skin Transplantation - immunology
Skin Transplantation - pathology
Time Factors
Transplantation, Homologous
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Summary:There is now considerable evidence suggesting that CD8(+) T cells are able to generate effector but not functional memory T cells following pathogenic infections in the absence of CD4(+) T cells. We show that following transplantation of allogeneic skin, in the absence of CD4(+) T cells, CD8(+) T cells become activated, proliferate, and expand exclusively in the draining lymph nodes and are able to infiltrate and reject skin allografts. CD44(+)CD8(+) T cells isolated 100 days after transplantation rapidly produce IFN-gamma following restimulation with alloantigen in vitro. In vivo CD44(+)CD8(+) T cells rejected donor-type skin allografts more rapidly than naive CD8(+) T cells demonstrating the ability of these putative memory T cells to mount an effective recall response in vivo. These data form the first direct demonstration that CD8(+) T cells are able to generate memory as well as effector cells in response to alloantigen during rejection in the complete absence of CD4(+) T cells. These data have important implications for the design of therapies to combat rejection and serve to reinforce the view that CD8(+) T cell responses to allografts require manipulation in addition to CD4(+) T cell responses to completely prevent the rejection of foreign organ transplants.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.176.4.2316