Experimental pancreatitis is characterized by rapid T cell activation, Th2 differentiation that parallels disease severity, and improvement after CD4(+) T cell depletion


Glaubitz, J., Wilden, A., van den Brandt, C., Weiss, F. U., Broker, B. M., Mayerle, J., Lerch, M. M., and Sendler, M. (2020). Pancreatology : official journal of the International Association of Pancreatology (IAP) [et al] 20



Abstract: 

Background: Acute pancreatitis is a gastrointestinal disorder of high incidence resulting in life threatening complications in up to 20% of patients. Its severe form is characterized by an extensive and systemic immune response. We investigated the role of the adaptive immune response in two experimental models of pancreatitis.

Methods: In C57BI/6-mice mild pancreatitis was induced by 8-hourly injections of caerulein and severe pancreatitis by additional, partial pancreatic duct ligation. T-cell-activation was determined by flow-cytometry of CD25/CD69, T-cell-differentiation by nuclear staining of the transcription-factors Tbet, Gata3 and Foxp3. In vivo CD4+ T-cells were depleted using anti-CD4 antibody. Disease severity was determined by histology, serum amylase and lipase activities, lung MPO and serum cytokine levels (IL-6, TNFα, IL-10).

Results: In both models T-cells were activated. Th1-differentiation (Tbet) was absent during pancreatitis but we detected a pronounced Th2/Treg (Gata3/Foxp3) response which paralleled disease severity in both models. The complete depletion of CD4+ T-cells via anti-CD4 antibody, surprisingly, reduced disease severity significantly, as well as granulocyte infiltration and pro- and anti-inflammatory cytokine levels. Co-incubation of acini and T-cells did not lead to T-cell-activation by acinar cells but to acinar damage by T-cells. During pancreatitis no significant T-cell-infiltration into the pancreas was observed.

Conclusion: T cells orchestrate the early local as well as the systemic immune responses in pancreatitis and are directly involved in organ damage. The Th2 response appears to increase disease severity, rather than conferring an immunological protection.