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


CONCLUSIONS
These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge.
Vora
Kalpit A
KA
Department of Immunology, Rahway, New Jersey 07065, USA. Kalpit.vora@spcorp.com
Porter
Gene
G
Peng
Roche
R
Cui
Yan
Y
Pryor
Kellyann
K
Eiermann
George
G
Zaller
Dennis M
DM
D000818:Animals; D000917:Antibody Formation / Q000276:immunology / Q000502:physiology*; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000502:physiology*; D007150:Immunohistochemistry; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D054873:Dipeptidyl-Peptidase IV Inhibitors; D018819:Dipeptidyl Peptidase 4