Salio Mariolina, Cella Marina, Vermi William, Facchetti Fabio, Palmowski Michael J, Smith Caroline L, Shepherd Dawn, Colonna Marco, Cerundolo Vincenzo
Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
Eur J Immunol. 2003 Apr;33(4):1052-62. doi: 10.1002/eji.200323676.
Plasmacytoid dendritic cells (PDC) are a small population of leukocytes specialized in the production of type I IFN. It has been shown that PDC have a potent T cell stimulatory capacity in allogeneic mixed lymphocyte reaction, However, their role in initiating primary immune responses remains elusive. We report that blood PDC efficiently prime naive CD8(+) lymphocytes specific for the melan-A(26-35) epitope to become IFN-gamma producing cells in vitro. In addition, we found that CD40L-stimulated PDC induce expression on primed melan-A-specific T cells of cutaneous lymphocyte antigen and L-selectin (CD62L), homing receptors that allow the migration of effector cells to the inflamed skin. Finally, we show that PDC can be found in the peri-tumoral area of most primary cutaneous melanomas in vivo and that type I IFN-containing supernatants derived from PDC increase melanoma cell surface expression of CD95 and MHC class I and class II molecules in vitro. Our results suggest a new immunomodulatory role for tissue infiltrating PDC, which may prime tumor-specific T cell responses and affect tumor growth via soluble factors.
浆细胞样树突状细胞（PDC）是一小群专门产生I型干扰素的白细胞。研究表明，PDC在同种异体混合淋巴细胞反应中具有强大的T细胞刺激能力，然而，它们在启动原发性免疫反应中的作用仍不清楚。我们报告称，血液中的PDC能在体外有效地使针对黑素A（26 - 35）表位的初始CD8⁺淋巴细胞致敏，使其成为产生γ干扰素的细胞。此外，我们发现CD40L刺激的PDC可诱导已致敏的黑素A特异性T细胞表达皮肤淋巴细胞抗原和L - 选择素（CD62L），这些归巢受体可使效应细胞迁移至炎症皮肤。最后，我们证明在体内大多数原发性皮肤黑色素瘤的肿瘤周围区域可发现PDC，并且PDC产生的含I型干扰素的上清液在体外可增加黑色素瘤细胞表面CD95以及MHC I类和II类分子的表达。我们的结果提示组织浸润性PDC具有一种新的免疫调节作用，其可能通过可溶性因子启动肿瘤特异性T细胞反应并影响肿瘤生长。
