Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance Journal Article
| Authors: | Pedicord, V. A.; Montalvo, W.; Leiner, I. M.; Allison, J. P. |
| Article Title: | Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance |
| Abstract: | CTLA-4, an Ig superfamily molecule with homology to CD28, is one of the most potent negative regulators of T-cell responses. In vivo blockade of CTLA-4 exacerbates autoimmunity, enhances tumor-specific T-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+ T-cell responses and the formation and maintenance of long-term CD8+ T-cell memory. In our studies, we show that during in vivo memory CD8+ T-cell responses to Listeria monocytogenes infection, CTLA-4 blockade enhances bacterial clearance and increases memory CD8 + 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+ T-cell priming leads to increased expansion and maintenance of antigen-specific memory CD8+ 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+ T-cell responses and support the possible use of CTLA-4-blocking antibodies during vaccination to augment memory formation and maintenance. |
| Keywords: | controlled study; nonhuman; cd8+ t lymphocyte; animal cell; mouse; animal tissue; cell function; cytotoxic t lymphocyte antigen 4 antibody; animal experiment; animal model; tumor necrosis factor alpha; gamma interferon; drug mechanism; single drug dose; cytokine production; cytotoxic t lymphocyte antigen 4; cell expansion; listeriosis; memory t lymphocyte |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 108 |
| Issue: | 1 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2011-01-04 |
| Start Page: | 266 |
| End Page: | 271 |
| Language: | English |
| DOI: | 10.1073/pnas.1016791108 |
| PROVIDER: | scopus |
| PMCID: | PMC3017182 |
| PUBMED: | 21173239 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: PNASA" - "Source: Scopus" |
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