Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T cells and macrophages. The clinical characteristics associated with this disease result from overproduction of Th1 cytokines including interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). In this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was detected in plasma in all patients (mean peak value, 30.0 ± 5.0 pg/mL), while IFN-γ was massively produced in nine patients (mean peak value, 79.2 ± 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma IL10 levels were elevated in all patients (mean peak value, 2,698.0 ± 3,535.0 pg/mL). There was a positive correlation between the levels of IFN-γ and IL-10 (P < .01). The plasma concentrations of these cytokines were initially high, before decreasing after the acute phase. However, the decrease in IL-10 levels was slower than that of IFN-γ. Although the concentration of IL-12 was high at the acute phase, in some patients, a peak in the level was delayed until the chronic phase. Thus, in HLH, production of cytokines that promote development of Th1 cells appears to be predominant over that for Th2 cell development. Overproduction of IL-10 was also observed indicating that a mechanism suppressing hyperactivation of Th1 cells and monocytes/macrophages functions in patients with this disease.

Dendritic cells (DCs) initiate and direct immune responses. Recent studies have defined different DC populations, therefore we undertook this study comparing 2 types of myeloid DCs: blood CD11c ؉ DCs and in vitro monocyte-derived DCs (MoDCs), which are both candidates as cellular adjuvants for cancer immunotherapy. Blood CD11c ؉ DCs were prepared by cell sorting from peripheral blood mononuclear cells cultured overnight in RPMI 1640 medium supplemented with autologous or pooled AB serum. Mo-DCs were prepared in the same medium using granulocyte macrophage-colony-stimulating factor (GM-CSF)/interleukin 4 (IL-4) and differentiated/activated with lipopolysaccharide or monocyte-conditioned medium (ActMo-DCs). Morphologically, differences between the DC preparations were noted both at a light and and electron microscopic level. Blood CD11c ؉ DCs expressed similar levels of HLA-DR, CD40, CD86, and CD83 as Mo-DCs. CD209 was present on Mo-DCs but not on blood CD11c ؉ DCs. Blood CD11c ؉ DCs generated a lower proliferative mixed leukocyte response (MLR) than Mo-DCs. Blood CD11c ؉ DCs loaded with 0.1 g/mL tetanus toxoid (TT)-generated greater T lymphocyte proliferative responses than did Mo-DCs or ActMo-DCs, but when loaded with higher TT concentrations no difference in T lymphocyte proliferative response was observed. Keyhole It has been accepted that DCs are produced in the bone marrow and migrate via the blood stream into virtually all tissues in the body. 1 These surveillance DCs capture antigen when appropriate and migrate to draining lymph nodes. The DCs process and present the antigen as major histocompatibility complex (MHC)-peptide complexes to antigen-specific naive T lymphocytes. The DCs responsible for these processes are thought to be myeloid DCs, but recent analyses have defined an additional blood "lymphoid" DC population. 4,5 Subsets of monocytes including CD16 ϩ CD14 ϩ , 6 and CD2 ϩ CD14 ϩ , 7 cells have also been identified as potential DC precursors. This new, and in some cases, conflicting, information regarding DC ontogeny makes it essential to clarify basic DC hematopoeitic development and also to define the functional properties of the different DC preparations proposed as immunotherapeutic cellular adjuvants. 3 DCs in the peripheral blood are identified within the HLA-DR ϩ , lineage (CD3, CD14, CD19, CD56) negative (Lin Ϫ ) blood mononuclear cell population. The precursors for the peripheral epithelial (CD1a hi ) and dermal (CD1a lo ) DCs 8 are identified within myeloid blood CD11c ϩ DCs. 9 The mix of lineage antibodies and the procedure used in purification of these cells influences the constitution of the myeloid blood DCs and new reagents now make it possible to define further subsets. 10 Certainly, CD14 ϩ monocytes incubated with granulocyte macrophage-colony-stimulating factor (GM-CSF)/interleukin 4 (IL-4) and subsequently differentiated/ activated with tumor necrosis factor alpha (TNF-␣) or other agents develop into monocyte-derived DCs (Mo-DCs) with many characteristics similar to the myelo...