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
Notes: --- - "Export Date: 4 March 2011" - "CODEN: PNASA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Ingrid Leiner
    49 Leiner
  2. James P Allison
    129 Allison