Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

BMC Immunol. 2009 Apr 9;10:19. doi: 10.1186/1471-2172-10-19.


Background: Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo.

Results: The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen.

Conclusion: These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge.

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Antibody Formation / physiology*
  • Dipeptidyl Peptidase 4 / immunology*
  • Dipeptidyl-Peptidase IV Inhibitors
  • Female
  • Flow Cytometry
  • Immunity, Cellular / physiology*
  • Immunohistochemistry
  • Immunologic Memory
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology


  • Dipeptidyl-Peptidase IV Inhibitors
  • Dipeptidyl Peptidase 4