Phenotype and function of dendritic cells and T-lymphocyte polarization in the human colonic mucosa and adenocarcinoma.
OBJECTIVE
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 (12million UI/day) (treated group; n=10) for 3days 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 naïve 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 naïve T cells were polarized toward a Th1 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 Th1 mediated anti-neoplastic response.
Gianotti
L
L
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy. Electronic address: luca.gianotti@unimib.it.
Sargenti
M
M
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy.
Galbiati
F
F
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy.
Nespoli
L
L
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy.
Brivio
F
F
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy.
Rescigno
M
M
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Nespoli
A
A
Department of Surgery, University of Milano-Bicocca, San Gerardo Hospital (5(o) piano A), Via Pergolesi 33, 20052 Monza, Italy.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D003082:Colectomy; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000970:Antineoplastic Agents; D007376:Interleukin-2