The expression of T-cell surface antigens CTLA-4, CD26, and CD28 is modulated by inhibition of dipeptidylpeptidase IV (DPP IV, CD26) activity in murine stress-induced abortions.
Inhibition of DPP IV has been shown to abrogate the stress-related increase in murine abortions and a concomitant increase in gamma-interferon. The aim of the present study was to investigate a potential impact of the DPP IV inhibitor Isoleucine Cyanopyrrolidide on the expression of surface antigens involved in T-cell responses. DBA/2-mated CBA mice were stressed on day 5.5 of pregnancy and received injections of a DPP IV inhibitor. On day 13 of gestation, the animals were sacrificed and the percentage of abortions was determined. As shown before, stress failed to boost the abortion rate in mice receiving the DPP IV inhibitor. In stressed animals, a lower surface density of CTLA-4 on decidual CD26-positive lymphocytes was observed than in non-stressed animals. Inhibition of DPP IV restored CTLA-4 surface density to normal and decreased surface expression of CD26 and CD28 on decidual lymphocytes irrespective of stress exposure. These observations suggest that a modulation of T-cell surface antigens expression due to inhibition of DPP IV activity may contribute to the potent anti-abortogenic effect observed here.
Rüter
Jens
J
Department of Medicine/Psychosomatics, Charité Campus Mitte, Humboldt University, Berlin, Germany. jens.reuter@charite.de
Hoffmann
Torsten
T
Heiser
Ulrich
U
Demuth
Hans Ulrich
HU
Arck
Petra C
PC
Klapp
Burghard F
BF
Hildebrandt
Martin
M
D000069594:Abatacept; D000022:Abortion, Spontaneous / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000276:immunology; D060908:CTLA-4 Antigen; D003656:Decidua / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000276:immunology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D013154:Spleen / Q000276:immunology; D013312:Stress, Physiological / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D004791:Enzyme Inhibitors; D018796:Immunoconjugates; D016753:Interleukin-10; D000069594:Abatacept; D007371:Interferon-gamma; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4