No abstract

Circulating human macrophages are often used to generate dendritic cells (DCs) by culturing them in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). As DCs are superb antigen-presenting cells, these types of myeloid DCs are now used in many DC-based vaccination protocols, especially in cancer, with the belief that they are essentially stimulatory or ‘immunogenic’. Here we show that just as peripheral macrophage-derived myeloid DCs can be stimulatory, in vitro cultures of myeloid DCs in GM-CSF and IL-4 followed by further maturation in interferon-γ plus bacterial superantigens (as DC maturing agents) can give rise to DCs that are functionally inhibitory. The stimulatory DCs express higher amounts of costimulatory molecules, synthesize IL-12, and efficiently stimulate naive allogeneic T cells in mixed lymphocyte reaction (MLR). The inhibitory DCs, in contrast, express lower concentrations of the critical costimulatory molecules, synthesize large amounts of IL-10, and are either marginally stimulatory or nonstimulatory in MLR. Moreover, while the stimulatory DCs further amplify proliferation of T cells in lectin-driven proliferation assays, the inhibitory DCs suppress T cell proliferation in similar assays, in vitro. Most interestingly, neutralization of the endogenously derived IL-10 with anti-IL-10 antibody with DC cultures as well as exposure of the inhibitory DCs to CpG oligonucleotides or to in vitro activated autologous CD4+ T helper cells repolarize them into stimulatory phenotype. Accordingly, these observations have important implications in translational research involving myeloid DCs.

The regulatory role of prolactin (Prl) on peripheral blood natural killer (NK) and lymphokine-activated killer (LAK) cell activities was studied in young (mean age, 40 years) and elderly (mean age, 68 years) healthy men and patients with carcinoma of the oral cavity (oral cancer). The peripheral blood NK cells, but not the LAK cells, were found to be depressed in oral cancer patients compared with age-matched healthy men. However, age-associated deficiency in both NK and LAK cell activity was observed in healthy men and cancer patients. Prl produced dosedependent inhibition (I, 10, 100 or 250 ng/ml) or stimulation (25-50 ng/ml) of resting NK cells in young groups of healthy men and cancer patients. In elderly groups less or no response of the NK cells to low doses of Prl (I-I 0 ng/ml) was evident. The NK cells of young and elderly healthy men were stimulated by human recombinant Interleukin-2 (rlL-2) (100 U/ml), and Prl (1-250 ng/ml) inhibited these cells. In oral cancer patients an altered response to low doses of Prl(1-50 ng/ml) was observed in IL-2-stimulated NK cells, which also revealed malignancyassociated loss of IL-2 response. In contrast, there was no malignancy or age-associated change in Prl response of the LAK cells. Treatment of peripheral blood lymphocytes of both healthy men and oral cancer patients for 5 days with Prl(50 ng/ml) in the presence of low concentration of serum generated LAK cells.o 1996 Wiley-Liss, Inc.

No abstract

The data suggest serious impairment of NK function in elderly patients with oral carcinoma. Generation of LAK activity with exogenous IL-2 could be an important modality of treatment in these patients.