Serum antigen(s) drive the proinflammatory T cell response in acute pancreatitis.
BACKGROUND
Immune cells and cytokines are central to the systemic inflammatory response syndrome and multiple organ failure associated with acute pancreatitis. The specific role of T cells in this response is unclear, and this study focused on evaluating T cell activation and its regulation in patients with acute pancreatitis.


METHODS
Peripheral blood samples of 14 patients with acute pancreatitis were obtained within 24 h of the onset of pain, within 48 h and at 1 week. T cell expression of surface markers CD69, CD62L and CD25 was measured. The production of interleukin (IL) 10 and IL-2 in vitro in response to the superantigen Staphylococcus enterotoxin B (SEB) was assessed. Serum samples from these patients were co-cultured with peripheral blood mononuclear cells from volunteers in the presence or absence of cytotoxic T lymphocyte-associated antigen (CTLA) 4 immunoglobulin, a specific inhibitor of antigen-dependent T cell activation.


RESULTS
Expression of CD69 was significantly increased in CD3(+) and CD4(+) populations at 48 h and 1 week, and on CD8(+) cells at 1 week. There was a significant increase in the production of SEB-induced IL-2 compared with findings in controls, but no significant IL-10 response. Serum from patients with pancreatitis activated normal T cells. This response was abolished completely by CTLA-4.


CONCLUSIONS
Acute pancreatitis results in the systemic activation of T cells. These cells are primed for a proinflammatory response to antigen stimulation and can be inhibited by antigen-specific T cell blockade. These data indicate that the immunoinflammatory response in acute pancreatitis is fueled by one or more serum antigens and offer prospects for further understanding of the aetiogenesis of pancreatitis.
Sweeney
K J
KJ
Academic Department of Surgery, St James's Hospital and Trinity College Dublin, Dublin, Ireland.
Kell
M R
MR
Coates
C
C
Murphy
T
T
Reynolds
J V
JV
D000208:Acute Disease; D000328:Adult; D017252:CD3 Complex / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000276:immunology*; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D008222:Lymphokines