Abstract
Rejection of immunogenic tumors is primarily mediated by T cells with both CD8+ cytolytic T cells (CTL) and CD4+ T helper cells (Th) playing important roles. There is compelling evidence that T cells require at least two signals to become fully activated. Signal one is generated by interaction between an antigen-specific receptor (TCR) on the T lymphocytes and antigenic peptide-MHC complexes on antigen-presenting cells (APC). Signal two is delivered by costimulatory molecules on the APCs to their counterreceptors on the T lymphocytes [1]. In the absence of costimulation, exposure to an antigen can lead to immunological ignorance in vivo [2] or anergy in some T cell clones [3].
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
DL Mueller, MK Jenkins, RH Schwartz, 1989: Clonal expansion versus functional clonal inactivation: A costimulatory signaling pathway determines the outcome of T cell antigen receptor occupancy. Annu. Rev. Immunol. 7, 445–480.
I Melero, N Bach, L Chen, 1997: Costimulation, tolerance and ignorance of cytolytic T lymphocytes in immune responses to tumor antigens. Life Sciences 60, 2035–2041
CH June, JA Bluestone, LM Nadler, CB Thompson, 1994: The B7 and CD28 receptor families. Immunol. Today 15, 321–331
PS Linsley, JA Ledbetter, 1993: The role of the CD28 receptor during T cell responses to antigen. Annu. Rev. Immunol. 11, 191–212
BE Bierer, WC Hahn, 1993: T cell adhesion, avidity regulation and signaling: a molecular analysis of CD2. Semin. Immunol. 5, 249–261.
KE Pollok, Pollok, YJ Kim, J Hurtado, Z Zhou, KK Kim, BS Kwon, 1994: 4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates anti-u-primed splenic B cells. Eur. J. Immunol. 24, 367–374
L Chen, PS Linsley, KE Hellström, 1993: Costimulation of T cells for tumor immunity. Immunol. Today 14, 483–486
L Chen, L, S Ashe, WA Brady, I Hellström, KE Hellström, JA Ledbetter, P McGowan, PS Linsley, 1992: Costimulation of antitumor immunity by the B7 counter-receptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71, 1093–1102
L Chen, P McGowan, S Ashe, JV Johnston, Y Li, I Hellström, KE Hellström, 1994: Tumor immunogenicity determines the effect of B7 co-stimulation on T cell-mediated tumor immunity. J. Exp. Med. 179, 523–532
Y Li, KE Hellstrom, SA Newby, L Chen, 1996: Costimulation by CD48 and B7–1 induces immunity against poorly immunogenic tumors. J. Exp. Med. 183, 639–644
EE Sercarz, PV Lehmann, A Ametani, G Benichou, A Miller, K Moudgil, 1993: Dominance and crypticity of T cell antigenic determinants. Annu. Rev. Immunol. 11, 729–766
JV Johnston, AR Malacko, MT Mizuno, P McGowan, I Hellström, KE Hellström, H Marquardt, L Chen, 1996: B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by MHC class I-re-stricted CD8+ cytolytic T lymphocytes. J. Exp. Med. 183, 791–800
L Chen, 1997: Immunological ignorance of silent antigen as an explanation for tumor evasion. Immunol. Today, in press
CA Smith, T Farrah, RG Goodwin, 1994: The TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death. Cell 76, 959–962
JC Hurtado, SH Kim, KE Pollok, ZH Lee, BS Kown, 1995: Potential role of 4-1BB in T-cell activation. Comparison with the costimulatory molecule CD28. J. Immunol. 155, 3360–3367
KE Pollok, SH Kim, BS Kwon, 1995: Regulation of 4-1BB expression by cell-cell interactions and the cytokines, interleukin-2 and interleukin-4. Eur. J. Immunol. 25, 488–494
WW Shuford, K Klussman, DD Tritchler, DT Loo, J Chalupny, AW Siadak, TJ Brown, J Emswiler, H Raecho, CP Larsen, TC Pearson, JA Ledbetter, A Aruffo, RS Mittler, 1997: 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J. Exp. Med. 186, 47–56
I Melero, WW Shuford, SA Newby, A Aruffo, JA Ledbetter, KE Hellström, RS Mittler, L Chen, 1997: Monoclonal antibodies against the 4-1BB T cell activation molecule eradicate established tumors. Nature Medicine 3, 682–685
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Chen, L. (1998). Overcoming T Cell Ignorance by Providing Costimulation. In: Walden, P., Trefzer, U., Sterry, W., Farzaneh, F., Zambon, P. (eds) Gene Therapy of Cancer. Advances in Experimental Medicine and Biology, vol 451. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5357-1_26
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5357-1_26
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7444-2
Online ISBN: 978-1-4615-5357-1
eBook Packages: Springer Book Archive