IntroductionDendritic cells (DCs) are important for the initiation of immune responses to foreign antigens because of their "professional" competence to capture and present antigen to T cells. The 2 functions, antigen uptake and presentation, are temporally and spatially separated. Thus, after antigen internalization, the DCs themselves undergo a process of maturation, migration, and relocation (for review, see Bell et al 1 ). During maturation, DCs up-regulate major histocompatibility complex (MHC), adhesion, and costimulatory molecules, including CD80 (B7.1), CD86 (B7.2), CD54 (ICAM-1), CD58 (LFA-3), CD11a, CD11c, and CD40, whereas they down-regulate the expression of Fc and mannose receptors. 2 Mature DCs also secrete high levels of interleukin-12 (IL-12), a Th-1-polarizing cytokine that promotes the maturation of cytotoxic T cells (CTLs). 3 Several viruses, such as herpes simplex virus, 4 measles virus, 5 and Epstein-Barr virus, have been shown to diminish DC function. Recently, hepatitis C virus (HCV) infection has also been shown to affect the function of DCs. Compared to monocyte-derived DCs from healthy donors, DCs from patients with chronic HCV infection showed impaired ability to stimulate allogeneic T cells and to produce interferon ␥ (IFN-␥). 6 An independent study also demonstrated impaired stimulatory capacity of DCs derived from HCV-infected patients with hepatocellular carcinoma. However, this dysfunction was not unique to HCV because DCs from hepatitis B virus-infected patients with hepatocellular carcinoma also showed reduced stimulatory activity, suggesting that the liver damage itself might affect DC function. 7 These studies examined only the DCs of patients with chronic HCV infection. To the best of our knowledge, studies investigating DC derived from patients with cleared HCV infection have not yet been reported.Hepatitis C virus causes an often inapparent acute infection that is cleared only in a minority of patients. 8 Patients who are able to clear the virus mount a vigorous T-cell response. Spontaneous viral clearance is correlated with both HCV-specific, IFN-␥-producing CD8 ϩ T cells and a strong proliferative CD4 ϩ T-cell response during the first 6 months after infection. 9 Similarly, patients who cleared the virus mounted a CTL response to a larger number of viral epitopes than those who became chronic carriers. 10 In addition, persistent CTL activity could be detected in patients whose HCV was resolved but not in patients with chronic HCV infection. 11 The clearance of an HCV infection has also been correlated with a strong HCV-specific T-helper cell response. [12][13][14] Because DCs are essential for T-cell activation, we questioned whether viral clearance was affected by their abilities to process and present antigen. We therefore compared DCs from chronically infected patients to those from patients who cleared the virus after a course of antiviral therapy and to those of healthy donors. DCs were generated in a 2-step protocol. 15 First, monocytes were isolated from peripheral...

Regeneration of hematopoiesis after allogeneic hematopoietic cell transplantation (HCT) involves conversion of the recipient's immune system to donor type. It is likely that distinct cell lineages in the recipient reconstitute at different rates. Dendritic cells (DCs) are a subset of hematopoietic cells that function as a critical component of antigen-specific immune responses because they modulate T-cell activation, as well as induction of tolerance. Mature DCs are transferred with hematopoietic grafts and subsequently arise de novo. Little information exists about engraftment kinetics and turnover of this cell population in patients after allogeneic HCT. This study examined the kinetics of DC chimerism in patients who underwent matched sibling allogeneic HCT. T-cell, B-cell, and myelocytic and monocytic chimerism were also studied. Peripheral blood cells were analyzed at defined intervals after transplantation from 19 patients with various hematologic malignancies after treatment with myeloablative or nonmyeloablative preparatory regimens. Cell subsets were isolated before analysis of chimerism. Despite the heterogeneity of the patient population and preparatory regimens, all showed rapid and consistent development of DC chimerism. By day ؉14 after transplantation approximately 80% of DCs were of donor origin with steady increase to more than 95% by day ؉56. Earlier time points were examined in a subgroup of patients who had undergone nonmyeloablative conditioning and transplantation. These data suggest that a major proportion of blood DCs early after transplantation is donor-derived and that donor chimerism develops rapidly. This information has potential implications for manipulation of immune responses after alloge-

The idiotype (Id) determinants on the multiple myeloma immunoglobulin can serve as tumor-specific antigens. An anti-Id immune response may stem the growth of the malignant clone. We report on 26 patients treated at our institution with high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) and vaccinated with the Id protein. The patients received chemotherapy and PBPCT to establish a minimal residual disease state. After high-dose therapy, the patients received a series of monthly immunizations consisting of 2 intravenous infusions of dendritic cells (DCs) pulsed with either Id protein or Id coupled with keyhole limpet hemocyanin (KLH) as an immunogenic carrier protein, followed by subcutaneous boosts of Id-KLH conjugates. DCs were obtained in all patients from a leukapheresis product 3 to 9 months after PBPCT. Patients were observed for toxicity, immune responses, and tumor status. The DC infusions and the administration of Id-KLH boosts were well tolerated, with patients experiencing only minor and transient side effects. Of the patients, 24 of 26 generated a KLH-specific cellular proliferative immune response. Only 4 patients developed an Id-specific proliferative immune response. Three of these immune responders were in complete remission at the time of vaccination. A total of 17 patients are alive at a median follow-up of 30 months after transplantation. Id vaccination with autologous DCs is feasible for myeloma patients after transplantation. Id-specific cellular responses can be induced in patients who are in complete remission. Further studies are needed to increase the rate of anti-Id immune responses in patients who do not achieve complete remission.