Pentoxifylline functions as an adjuvant in vivo to enhance T cell immune responses by inhibiting activation-induced death

Radhakrishnan Suresh, Monika Vig, Sumeena Bhatia, Eric P B Goodspeed, Beena John, Usha Kandpal, Smita Srivastava, Anna George, Ranjan Sen, Vineeta Bal, Jeannine M. Durdik, Satyajit Rath

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Abstract

Modalities for inducing long-lasting immune responses are essential components of vaccine design. Most currently available immunological adjuvants empirically used for this purpose cause some inflammation, limiting clinical acceptability. We show that pentoxifylline (PF), a phosphodiesterase (PDE) inhibitor in common clinical use, enhances long-term persistence of T cell responses, including protective responses to a bacterial immunogen, Salmonella typhimurium, via a cAMP-dependent protein kinase A-mediated effect on T cells if given to mice for a brief period during immunization. PF inhibits activation-mediated loss of superantigen-reactive CD4 as well as CD8 T cells in vivo without significantly affecting their activation, and inhibits activation-induced death and caspase induction in stimulated CD4 as well as CD8 T cells in vitro without preventing the induction of activation markers. Consistent with this ability to prevent activation-induced death in not only CD4 but also CD8 T cells, PF also enhances the persistence of CD8 T cell responses in vivo. Thus, specific inhibition of activation-induced T cell apoptosis transiently during immune priming is likely to enhance the persistence of CD4 and CD8 T cell responses to vaccination, and pharmacological modulators of the cAMP pathway already in clinical use can be used for this purpose as immunological adjuvants.

Original languageEnglish (US)
Pages (from-to)4262-4272
Number of pages11
JournalJournal of Immunology
Volume169
Issue number8
StatePublished - Oct 15 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Suresh, R., Vig, M., Bhatia, S., Goodspeed, E. P. B., John, B., Kandpal, U., Srivastava, S., George, A., Sen, R., Bal, V., Durdik, J. M., & Rath, S. (2002). Pentoxifylline functions as an adjuvant in vivo to enhance T cell immune responses by inhibiting activation-induced death. Journal of Immunology, 169(8), 4262-4272.