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

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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 8 Pg. 4262-72 (Oct 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12370357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, Bacterial
• Epitopes, T-Lymphocyte
• Cyclic AMP-Dependent Protein Kinases
• Pentoxifylline

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacology)
• Animals
• Antigens, Bacterial (immunology)
• Apoptosis (drug effects, immunology)
• CD4-Positive T-Lymphocytes (cytology, drug effects, immunology)
• CD8-Positive T-Lymphocytes (cytology, drug effects, immunology)
• Cells, Cultured
• Clone Cells
• Colony-Forming Units Assay
• Cyclic AMP-Dependent Protein Kinases (physiology)
• Epitopes, T-Lymphocyte (analysis)
• Immunization
• Immunologic Memory (drug effects)
• Injections, Subcutaneous
• Lymphocyte Activation (drug effects)
• Lymphocyte Count
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Pentoxifylline (administration & dosage, immunology, pharmacology)
• Salmonella typhimurium (immunology)
• T-Lymphocyte Subsets (cytology, drug effects, immunology, microbiology)