T-cell vaccination in Crohn's disease: principles and presentation of the first two cases.
In Crohn's disease (CD) CD4(+) T-cells producing tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important for disease progression. T-cell vaccination with such attenuated (gamma-irradiated) CD4(+) T cells may ameliorate the auto-reactive actions of Type-1 T cells through stimulation of interleukin-10 (IL-10)-producing regulatory T cells. This study aimed to propagate and use gut-derived type-1 CD4(+) T-cells for vaccination in CD. In a case study, two patients with CD-activity index (CDAI) >150 for >1 year were vaccinated with 800 x 10(6) attenuated autologous gut-derived CD4(+) T cells producing Type-1 cytokine -- grown in the presence of high concentrations of only IL-2 and IL-4. The T-cell vaccination was safe, causing only minor redness and tenderness at the injection sites. In Case 2, the treatment brought 3-years with active steroid-resistant CD into remission. CDAI dropped from 171 to 76, CD-endoscopic index of severity fell from 20 to eight and C-reactive protein reduced from 165 to 70 nmol/L. Case 1 received rescue infliximab (there was disease progression before sufficient quantities of cells were ready for the second vaccination). We concluded that it is possible to propagate T cells for autologous vaccination for CD and that treatment was safe. One patient, vaccinated according to the protocol, improved with sustained result for >1 year.
Agnholt
Jørgen
J
Department of Medicine V, Aarhus University Hospital, University of Aarhus, Denmark. jorge@akh.aaa.dk
Kaltoft
Keld
K
Jakobsen
Niels O
NO
Dahlerup
Jens F
JF
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000069285:Infliximab; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D014611:Vaccination
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D000069285:Infliximab