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Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 1/4/2011, Vol. 108 Issue 1, p266-271, 6p, 4 Graphs
- Publication Year :
- 2011
-
Abstract
- CTLA-4. an lg superfamily molecule with homology to CD28, is one of the most potent negative regulators of 1-cell responses. In vivo blockade of CTLA-4 exacerbates autoimmunity, enhances tumor specific 1-cell responses, and may inhibit the induction of T-cell anergy. Clinical trials of CTLA-4-blocking antibodies to augment T-cell responses to malignant melanoma are at an advanced stage; however, little is known about the effects of CTLA-4 blockade on memory CD8<superscript>+</superscript> T-cell responses and the formation and maintenance of long-term CD8<superscript>+</superscript> T-cell memory. In our studies, we show that during in vivo memory CD8<superscript>+</superscript> T-ceIl responses to Listeria monocy- to genes infection, CTLA-4 blockade enhances bacterial clearance and increases memory CD8<superscript>+</superscript> T-cell expansion. This is followed by an accumulation of memory cells that are capable of producing the effector cytokines IFN-γ and TNF-α. We also demonstrate that in a vaccination setting, blocking CTLA-4 during CD8<superscript>+</superscript> T-cell priming leads to increased expansion and maintenance of antigen-specific memory CD8<superscript>+</superscript> T-cells without adversely affecting the overall T-cell repertoire. This leads to an increase in memory cell effector function and improved protective immunity against further bacterial challenges. These results indicate that transient blockade of CTLA-4 enhances memory CD8<superscript>+</superscript> T-cell responses and support the possible use of CTLA-4-blocking antibodies during vaccination to augment memory formation and maintenance. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
AUTOIMMUNITY
IMMUNITY
CYTOKINES
LISTERIA monocytogenes
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 108
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 58666883
- Full Text :
- https://doi.org/10.1073/pnas.1016791108