Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)–dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II–positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)γ–producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Aβ b, expression is restricted to CD11b+ and CD8α+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II–negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNγ. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8α+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.

Summary Granulocyte colony-stimulation factor (G-CSF) is a cytokine that selectively promotes growth and maturation of neutrophils and may modulate the cytokine response to inflammatory stimuli. The purpose of this study was to examine the effect of G-CSF on ex vivo peripheral blood mononuclear cell (PBMC) functions. Ten patients with breast cancer were included in a clinical trial in which r-metHuG-CSF was administrered daily for 5 days to mobilize peripheral blood stem cells. Ten healthy women were also included as controls. Our data show that G-CSF treatment induces an increase in peripheral blood leucocyte, neutrophil, lymphocyte and monocyte counts. We have found a modulation in the percentages of CD19+, CD45+CD14+, CD4+CD45RA+ and CD4+CD45RO+ cells in PBMC fractions during G-CSF treatment. We have also found a significant reduction in the proliferative response of PBMC to mitogenic stimulation that reverted 14 days after the fifth and the last dose of G-CSF. Furthermore, it was not associated with significant changes in the pattern of cytokine production. The mechanism of this immunoregulatory effect is probably indirect since G-CSF receptor has not been found in T lymphocytes. This mechanism and its potential clinical applications remain to be elucidated.

The purpose of this work was to investigate the clinical significance of serum levels of proinflammatory cytokines in pediatric patients undergoing cardiopulmonary bypass. We divided the patients in two groups: 8 neonates, and 19 non-newborn children. IL-1beta, IL-6, IL-8, and TNF serum levels were quantified before sternotomy, at admission to the PICU (30 min postoperatively), 24 h after the onset of surgery and 3 days after the operation. Surgical cardiac stress elicits significant increments of IL-6, IL-8 and TNF serum concentrations in both neonates and non-neonates, regardless of their preoperative clinical condition. However, in newborns the magnitude of the proinflammatory cytokine increments was, in particular with IL-8, remarkably greater than in older children. Moreover, neonate and non-neonate patients showed clearly disparate patterns of serum concentrations over time of both IL-8 and TNF. There was a marked relationship between IL-8 levels and postoperative morbidity, evaluated by pulmonary dysfunction, days on inotropic support and days of PICU stay in both neonates and non-neonates patients. In contrast, we found no relationship between serum levels of IL-6 and TNF and postoperative clinical data. Newborn and non-newborn patients undergoing cardiopulmonary bypass exhibit dissimilar patterns of proinflammatory cytokines. IL-8 might be implicated in the multiorganic dysfunction related to cardiopulmonary bypass in pediatric patients.

To determine if activation-induced cytokine production is altered in CD2+ lymphocytes from B-CLL patients, cytokine levels were determined by ELISA in supernatants of PHA-stimulated cultures of CD2+ cells from 33 B-CLL patients and 22 healthy controls. The production of Interferon gamma (IFN-gamma) and Tumor Necrosis Factor (TNF-alpha) by mitogen-activated CD2+ lymphocytes from B-CLL patients was higher than that found in healthy controls, while no differences were found in TNF-beta production. IFN-gamma and TNF-alpha levels determined at 72 h in PHA-stimulated CD2+ cell cultures from B-CLL patients statistically correlated with the percentages of CD3+CD45RO+ and CD3-CD56+ lymphocytes, respectively. Although there were differences in the production kinetics of interleukins (ILs) 2 and 4 between B-CLL patients and the healthy controls, no differences were found at the time when the levels of both interleukins peak. The production of both IFN-gamma and IL-4 by PHA-stimulated CD2+ lymphocytes from non-smouldering B-CLL patients was significantly higher than that from smouldering B-CLL patients while no significant differences were found in the production of IL-2, TNF-alpha, and TNF-beta between the two B-CLL patient groups. These data suggest that functional alterations in the production of cytokines by CD2+ cells from B-CLL patients could help to explain the expansion of leukemic cells in B-CLL patients.

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