Phenotype and function of dendritic cells and T-lymphocyte polarization in the human colonic mucosa and adenocarcinoma

Aim: To evaluate the status of activation of the intestinal dendritic cells (DCs) and T lymphocytes (T cells) from surgical specimens of human colon and adenocarcinoma, and the potential effect of administration of interleukin 2 (IL-2). Methods: Patients undergoing colectomy for cancer were randomized to receive subcutaneous IL-2 (12 million Ul/day) (treated group; n = 10) for 3 days before operation or no treatment (control group, n = 10). DCs and T cells were isolated and purified from the lamina propria (LP) of segments of normal colon and adenocarcinoma of both groups. Cell phenotype was determined by expression of membrane receptors. Interaction between DC and T cells was assesses by a mixed leukocyte reaction using naive T cells co-cultured with DCs. CD4+ T-cell polarization was studied by intracellular staining with monoclonal antibodies for interleukin-4 and interferon-gamma. Results: CD4+ T cells were significantly less in tumour than in LP (p < 0.05) in both treated and control groups. IL-2 did not modify the number of any of the T-cell subsets analysed. In contrast, T cells isolated from LP and neoplasm of treated patients produced more interferon-gamma and less interleukin-4 (p < 0.05 vs. controls). IL-2 administration significantly increased (p < 0.05) the number of mature, myeloid and plasmocytoid DCs compared to controls. Allogeneic naive T cells were polarized toward a Thl type of response which appeared to be mediated by IL-2 activated DCs. Conclusions: systemic IL-2 treatment may have immunomodulatory properties on intestinal DC maturation and drive a Thl mediated anti-neoplastic response. (c) 2008 Elsevier Ltd. All rights reserved.