Immunoglobulin-secreting cells in healthy peripheral blood mononuclear cells

Immunoglobulin-secreting cells were measured in healthy uncultured peripheral blood mononuclear cells (PBMCs) in vitro. The percentage of IgM-, IgG- and IgA-secreting cells in adult PBMCs was 0.053, 0.099 and 0.065%, respectively. The percentage of IgM-, IgG- and IgA-secreting cells was 0.73, 5.2 and 3.8% of surface IgM-, IgG- and IgA-bearing cells, respectively. The numbers of IgM-, IgG- and IgA-secreting cells increased with age in childhood. However, the numbers of all three classes were slightly decreased in adults compared with children aged 9-15 years. These results may explain the difference in immunity in vivo.     

外周血循环肿瘤细胞检测的研究进展

Metastasis usually presents in the different courses of tumor diseases and associates with poor prognosis. Cir-culating tumor cells (CTC) are considered to be essential for conforming metastasis and can be detected in tumor patients' peripheral blood. CTC are not easily detected by conventional cytology methods because of their low frequency in peripheral blood. Our article reviews the recent research results on this subject, and also discusses the problems and prospects in this area.     

Mobilization of peripheral blood stem cells in advanced ovarian cancer

High-dose chemotherapy with hematopoietic support has been expected to improve the survival of advanced ovarian cancer patients in recent years. An essential component of such treatment has been the ability to collect and reinfuse a large number of peripheral blood stem cells (PBSCs) following high dose therapy. This study was designed to determine which clinical and hematological factors would be better indicators to collect the proper volume of PBSCs. Thirteen patients received a total of 24 courses of induction chemotherapy and 69 of apheresis. We usually mobilized stem cells using CEP chemotherapy (cisplatin 50-70 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 1.5 g/m2) with G-CSF and CEE regimen (cyclophosphamide 2.0 g/m2, epirubicin 50 mg/m2, and etoposide 50 mg/m2) as a salvage for mobilization. We obtained an average 5 x 10(6)/kg of CD34+ cells for 3 days as one course. The number of CD34+ cells collected significantly depended on the platelets and reticulocytes on the first day of apheresis, but not a nadir of WBCs. It is concluded that apheresis should be started on recovery of WBCs to 5,000-10,000/microliters, of immature granulocytes to > or = 10% and of reticulocytes to > or = 20%. This study confirmed the feasibility of collecting enough PBSCs to use standard chemotherapy of ovarian cancer patients.     

The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells

In this study we examined the effects of retinol (ROH), a metabolic precursor of retinoic acid (RA), on Staphylococcus aureus Cowan I (SAC)-induced immunoglobulin synthesis of cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC). ROH augmented SAC-induced IgM synthesis of CBMC by 5.9 +/- 1.5-fold (n = 7, mean +/- s.d.), and IgG synthesis of adult PBMC by 16.3 +/- 5.1-fold (n = 3) at optimal concentrations of 10(-6) M and 10(-11) M, respectively. No augmenting effects could be demonstrated for the other immunoglobulin isotypes. Time-course studies showed that the synthesis of IgM by CBMC was accelerated with detectable immunoglobulin in supernatant fluids starting on day 3. ROH augmented immunoglobulin synthesis of CBMC stimulated by Epstein-Barr virus (EBV), a T cell-independent polyclonal activator, and of EBV-transformed B cell clones (2.5 +/- 0.2 and 4.1 +/- 1.5-fold increase, respectively), which suggests that ROH can act directly on B cells to enhance immunoglobulin synthesis. In contrast, when ROH was preincubated with cord blood T cells, washed and added to the B cell-enriched fraction with SAC, no increase (0.9-1.8-fold) in IgM synthesis was obtained. Thus, the principal mechanism(s) by which ROH augments immunoglobulin synthesis is by acting on B cells. This is in contrast to the immunoglobulin-enhancing effects of RA which is mediated by T cells, or T cell products, e.g. cytokine. Our studies suggest that RA and ROH may have different pathways of immunoglobulin-enhancing effects, perhaps mediated by different retinoid binding proteins resulting in gene activation and immunoglobulin synthesis.     

Reactive oxygen species activate human peripheral blood dendritic cells

This study investigates the effects of hydrogen peroxide, a potent oxygen free radical donor, on the phenotype and function of dendritic cells differentiated from peripheral blood precursors. We report that hydrogen peroxide induces an up-regulation of several dendritic cell surface markers involved in interaction with T cells, including MHC Class II molecules (DQ and DR) and the co-stimulatory molecules CD40 and CD86. Moreover we have observed that H2O2-treated dendritic cells are more efficient in promoting T cell proliferation than normal dendritic cells and that this enhancement can be blocked using the free radical scavenger agent N-acetylcysteine. Oxygen free radicals are a common by-product of inflammation, and our results suggest they may play an important role in activation of sentinel dendritic cells, linking tissue damage to the initiation of an adaptive immune response.     

The photodynamic effect of Victoria blue BO on peripheral blood mononuclear and leukemic cells

The photodynamic effect of Victoria blue BO (VB-BO) and photoirradiation on peripheral blood mononuclear cells was studied. The cells were preincubated with VB-BO followed by photoirradiation and overnight culture. The highest percentage of dead cells (propidium iodide assay in flow cytometry) was seen in the monocyte population. The lymphocytes showed a lower sensitivity to VB-BO photodynamic action than the monocytes (12% vs 80% of PI-positive cells). The effect of VB-BO and phototreatment on lymphocyte function was studied using a mitogen-induced proliferation assay. A decrease of mitogen response was observed. The VB-BO and photoirradiation were also used on leukemic cells. The leukemic cells from acute myeloid leukemia and B precursors leukemia were sensitive to VB-BO photodynamic action. The high VB-BO sensitivity of monocytes and leukemic cells (myeloid and lymphoid B derived) suggests possible application of VB-BO for selective depletion of monocytes or sensitive leukemic cells.     

Phenotype and engraftment potential of cytokine-mobilized peripheral blood mononuclear cells

Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard-to-fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton-like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle-specific actin, and alpha smooth muscle actin, whereas cytokeratin, S-100 protein, EMA, CEA, and desmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear-cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear-cell neoplasms of the skin.     

Influence of serum micronutrients on the incidence of kinetochore-positive or -negative micronuclei in human peripheral blood lymphocytes

The possible contribution of some selected serum micronutrients (beta-carotene, vitamins B12 and C, folic acid and alpha-tocopherol) to spontaneous chromosomal damage was investigated in human peripheral blood lymphocytes from 33 non-smoking healthy donors by the cytokinesis-block micronucleus assay. Labelling of micronuclei with antikinetochore serum was used to discriminate between kinetochore-positive and -negative micronuclei and thus between micronuclei which arise from whole chromosome loss and those which arise from chromosome breaks. Simple correlation analysis showed that age was significantly associated with the increased frequency of micronucleated cells, and this age-related increase in these cells was due to the increase in cells with both kinetochore-positive and -negative micronuclei. Serum micronutrient levels had no apparent significant effects on incidence of micronucleated cells except for the weak positive correlation between vitamin B12 levels and frequency of kinetochore-positive micronucleated cells. Multiple regression analysis with age and serum micronutrient levels as independent variables showed that (a) age was the most influential variable for the frequency of micronucleated cells, (b) the serum vitamin C level was associated with increased frequency of spontaneous micronucleated cells, and this increase was mainly due to the increase in cells with kinetochore-positive micronuclei, and (c) the serum folic acid level was significantly and negatively related to the frequencies of cells with both kinetochore-positive and -negative micronuclei. To avoid the predominant age-effect, we also performed separate multiple regression analysis with age-adjusted frequency of micronucleated cells as dependent variable. The results from this analysis again showed a significant and positive effect of serum vitamin C level on age-adjusted frequency of kinetochore-positive micronucleated cells, while marginal negative effect of folic acid on age-adjusted frequency of total micronucleated cells (P < 0.06) and kinetochore-positive micronucleated cells (P < 0.051) was detected. These results suggest that age and serum vitamin C are definitely variables for frequencies of spontaneous chromosome loss, and that serum folic acid is perhaps another important micronutrient which influence the frequency of spontaneous chromosomal damage.     

Age-related loss of immunoregulatory function in peripheral blood CD8 T cells

This article considers the value of export controls in reducing the threat of biological weapons. It concludes that export control through export licensing is an essential element in the overall strategy to limit the spread of biological weapons. Modifications to existing export control systems can maximize the usefulness of export controls for limiting the threat of biological warfare and bioterrorism. Export controls are useful only within a broader strategy that includes both an arms control dimension and military defensive preparedness.     

Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations of Bruton tyrosine kinase (Btk); Btk plays an essential role in the development of mature B cells. However, small numbers of B cells ("leaky B cells") are present in the peripheral blood of most XLA patients. In this study, we analyzed the function of these leaky B cells obtained from XLA patients. Enough numbers of B cells were available for analysis from five of nine XLA patients originally screened. Sequence analysis revealed missense mutations of Btk in four of the five XLA patients. No mutation was found in the coding region of Btk in one patient. Western blotting and/or flow cytometric analysis failed to detect Btk protein in all five patients. B cells isolated from peripheral blood of these XLA patients were CD5-, CD20+, CD19+, and CD21-. If stimulated with anti-CD40 and IL-4, XLA B cells proliferated normally and produced significant amounts of IgE. Anti-CD40 stimulation of XLA B cells resulted in normal expression of CD23. In addition, three of the five XLA patients studied were immunized with bacteriophage phiX174 and produced low but detectable levels of antiphage-specific Ab. Similarly, X-linked immunodeficiency mice, which carry a missense mutation in Btk, produced substantial amounts of antiphage Ab. These results indicate that CD40 signaling is intact in B cells lacking demonstrable Btk, and that leaky B cells in XLA patients can proliferate, undergo isotype switching, and differentiate into specific Ab-producing cells.     

Suppression of HIV-1 replication in peripheral blood mononuclear cells by fasudil

Fasudil is a potent inhibitor for various protein kinases such as myosin light chain kinase and protein kinase C. It has been used as a drug for improvement of intracranial vasospasm and following ischaemic diseases. In this report, we demonstrate that fasudil suppressed the replication of human immunodeficiency virus type 1 (HIV-1) in mitogen-activated peripheral blood mononuclear cells. Our finding shows that fasudil may be useful as a new and distinct chemotherapeutic agent against HIV-1 infection.     

The role of granulocyte colony-stimulating factor in mobilization and transplantation of peripheral blood progenitor and stem cells

The article provides a review of the role of granulocyte colony-stimulating factor (G-CSF) for mobilization and transplantation of peripheral blood progenitor and stem cells. Recombinant gene technology has permitted the production of highly purified material for therapeutic use in humans. Progenitor cells can be assessed using semisolid and liquid culture assays or direct immunofluorescence analysis of cells expressing CD34. This antigen is found on lineage-determined hematopoietic progenitor cells as well as on more primitive stem cells with extensive self-renewal capacity. Administration of G-CSF during steady-state hematopoiesis or following cytotoxic chemotherapy leads to an increase of hematopoietic progenitor cells in the peripheral blood. The level of circulating CD34+ cells post-chemotherapy is greater compared with G-CSF administration during steady state. On the other hand, CD34+ cells harvested post-chemotherapy contain a smaller proportion of more primitive progenitor cells (CD34+/HLA-DR- or CD34+/CD38-) compared with G-CSF treatment alone. Independent of the mobilization modality, the amount of previous cytotoxic chemo- and radiotherapy adversely affects the yield of hematopoietic progenitor cells. While continuous subcutaneous administration of G-CSF between 5 and 16 micrograms/kg bodyweight is preferred, additional dose-finding studies may be helpful to optimize current dose schedules. Adhesion molecules like L-selectin, VLA (very late antigen)-4 and LFA (leukocyte function antigen)-1 are likely to play a role in mobilization, since these antigens are expressed on CD34+ cells from bone marrow in different densities compared with blood-derived CD34+ cells collected following G-CSF-supported cytotoxic chemotherapy. It is also relevant for transplantation that during G-CSF-enhanced recovery post-chemotherapy, peripheral blood is enriched with a greater proportion of CD34+ cells expressing Thy-1 in comparison with CD34+ cells from bone marrow samples obtained on the same day or before the mobilization therapy was started. The early nature of the CD34+/Thy-1+ cells is very likely since this phenotype has been found on stem cells from human fetal liver and bone marrow and on cord blood cells. As a result, G-CSF-mobilized blood stem cells provide rapid and sustained engraftment following high-dose therapy, including myeloablative regimens. Positive selection of CD34+ cells as well as ex vivo expansion using different cytokines are currently being investigated for purging and improvement of short-term recovery post-transplantation. Future developments include the use of blood-derived hematopoietic stem cells for somatic gene therapy. The availability of growth factors has been an important prerequisite for the development of these new avenues for cell therapy.     

G-CSF-mobilized CD34 peripheral blood stem cells are significantly less apoptotic than unstimulated peripheral blood CD34 cells: role of G-CSF as survival factor

Vi bacterial polysaccharide is a homopolymer of alpha 1-4 N-acetyl polygalacturonic acid with variable O-acetylation at position C-3 and forms a capsule around many bacteria. It has been referred to as the virulence factor of Salmonella typhi and is also a candidate vaccine against typhoid fever. The present study reports the interaction of this polysaccharide with murine mononuclear phagocytes and lymphocytes, and with human monocytes. Vi showed a dose-dependent binding to the murine monocyte cell lines WEHI-274.1 and J774. This binding was abrogated if the polysaccharide was deacetylated, suggesting involvement of acetyl groups in this interaction. Vi also bound to the murine B-cell lymphoma line A20, to peritoneal exudate cells and to a lesser degree to spleen cells and thymocytes from BALB/c mice. The polysaccharide also interacted with the human histiocytic lymphoma line U937 but not with the human monocyte cell line THP-1. Stimulation with Vi led to up-regulation of surface major histocompatibility complex (MHC) class II expression on A20 cells. Immunoprecipitation of Vi-bound molecules from cell surface biotinylated A20 and WEHI-274.1 revealed two bands with MW of about 32,000 and 36,000. The study demonstrates that Vi capsular polysaccharide can interact with mononuclear phagocytes and lymphocytes through specific cell surface molecules and modulate MHC class II expression.     

Inhibition effect of shengma-gegen-tang on measles virus in Vero cells and human peripheral blood mononuclear cells

The nucleotide sequence of gene 6 encoding the rotavirus major capsid protein VP6 of EDIM strain (EW) was determined and compared to that of 20 previously reported strains with known subgroup specificities. Multiple alignments of amino acid sequences exhibited a high level of sequence conservation (87 to 99.2%). Site-specific mutagenesis experiments were undertaken to localize regions involved in subgroup specificity. Amino acid positions 305, 315, and a region 296-299 (or 301 for equine strain H-2) were identified as contributing to subgroup epitopes. A single amino acid mutation at position 305 or 315 was sufficient to change the subgroup specificity of EW VP6 protein from non I/II to subgroup I- or subgroup II-like, respectively. Mutation at these sites may be another important mechanism for subgroup variation, along with gene reassortment.     

Proliferation of human peripheral blood mononuclear cells during calcium channel blockade

To evaluate the role of intracellular calcium and particularly Ca2+ uptake in the initiation of lymphocyte mitogenesis, the effect of mibefradil--which blocks both L- and T-type calcium channels with a more selective blockade of T-type channels--on the proliferation of human peripheral blood mononuclear cells (PBMC) is compared with the effect of nifedipine, which blocks only the L-type calcium channel. The rate of 3H-thymidine, 3H-uridine, and 3H-leucine incorporation into control and concanavalin A-stimulated PBMC in the presence or absence of the calcium channel blockers mibefradil or nifedipine (1, 10, or 50 micromol/L), and of the intracellular calcium antagonist TMB-8 or the calmodulin antagonist W-7 (1, 10, 25, or 50 micromol/L) was assayed in cells cultured for 3 days. The cellular cytotoxicity and the cell number in growing cultures was also determined in mibefradil- or nifedipine-treated control or stimulated cells. Mibefradil and nifedipine reduced the cell number and the 3H-thymidine, 3H-uridine, or 3H-leucine incorporation or the de novo DNA, RNA, or protein synthesis in control and concanavalin A-stimulated human PBMC in a concentration-dependent manner. Mibefradil exhibited a more pronounced inhibition than nifedipine. The inhibitory effect of mibefradil or nifedipine on DNA synthesis was dependent upon the timing of treatment with the drugs. The inhibitory effect of mibefradil or nifedipine on the lymphoproliferative response was nearly abolished if the drugs were added 20 h after cell stimulation. A markedly reduced inhibitory effect was found when mibefradil or nifedipine were added 1 to 7 h after cell stimulation. However, regardless of time of addition, TMB-8 and W-7 caused a persistent inhibition of the proliferation of human PBMC. Our data show that mibefradil had a more pronounced inhibitory effect on the proliferation of human PBMC than nifedipine and that this inhibitory effect on de novo DNA synthesis was dependent upon the timing of treatment with both drugs. Mibefradil and nifedipine also reduce RNA and protein synthesis in human PBMC. Therefore, administration of these calcium channel blockers to inhibit cellular proliferation might be most beneficial at anatomic sites where cellular proliferation is not already an active process, while being ineffective in the presence of ongoing active proliferation, as suggested by some prospective studies.     

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.     

High incidence of chronic graft versus host disease after allogeneic peripheral blood progenitor cell transplantation. The Spanish Group of Allo-PBPCT

BACKGROUND AND OBJECTIVE: The incidence of acute GVHD (aGVHD) in allogeneic peripheral blood progenitor cell transplantation (allo-PBPCT) seems to be similar to that seen in allogeneic bone marrow transplantation (allo-BMT). In contrast, some preliminary results suggest that the incidence of chronic GVHD (cGVHD) might be higher. The aim of the present study was to analyze the actuarial probability of developing cGVHD in allo-PBPCT, its clinical manifestations and response to treatment. METHODS: We have retrospectively analyzed clinical results from 21 allo-PBPCT recipients that had been transplanted at least 18 months before this study and that fulfilled the following criteria: HLA identical sibling donor, non T-cell depleted apheresis and more than 90 days of survival with sustained engraftment. The median follow-up was 12 months (range 4.5-22). RESULTS: Twelve out of the 21 (57%) patients presented cGVHD, 1 limited and 11 extensive. The actuarial probability of cGVHD was 72.7% (95% CI, 49-96%). The median interval from transplant to onset was 180 days (range 95-270). Nine of the 12 cases (75%) presented combined skin and liver involvement. Of the other three, the liver was involved in one case; skin, mouth, and nail cGVHD was observed in another case; and skin and mouth involvement together with an obstructive pulmonary disease was observed in the remaining case. Under therapy, a complete resolution of cGVHD manifestations was achieved in five cases, and a partial improvement was attained in three other cases. In two responsive patients, cGVHD reappeared after stopping treatment. Four patients were refractory to the treatment. INTERPRETATION AND CONCLUSIONS: It would appear from this retrospective and multicenter study that, after a median follow-up of 12 months, cGVHD after allo-PBPCT could be more frequent than after allo-BMT. A randomized trial with a large number of patients and a sufficient follow-up will be necessary to answer this question definitively.     

A cryopreservation method of human peripheral blood mononuclear cells for efficient production of dendritic cells

We studied whether inducers of cell differentiation alone could have cytotoxic effect on the promonocytic U937 and Mono Mac 6 cells in vitro. The cells were incubated with standard differentiating doses of interferon (IFN)-gamma, dibutyryl cAMP (Bt2cAMP) or the phorbol ester phorbol-12-myristate-13-acetate (PMA), with or without lipopolysaccharide (LPS), and both protein synthesis and viability were examined. In both U937 and Mono Mac 6 cells the incorporation of [3H]leucine was significantly reduced after PMA plus LPS stimulation, but not after IFN-gamma stimulation, when compared with controls. For U937 cells there was also reduced incorporation after Bt2cAMP stimulation. Trypan blue exclusion experiments and the number of cells remaining in the cultures indicated that Bt2cAMP-, PMA- and/or LPS-stimulated, but not IFN-gamma-stimulated, cells were less viable than unstimulated U937 or Mono Mac 6 cells. The results suggest that Bt2cAMP, PMA and LPS, but not IFN-gamma, are cytotoxic towards promonocytic cancer cell lines in vitro.     

The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses

Peripheral blood dendritic cells (DC) produce IFN-alpha in response to challenge by many enveloped viruses including herpes simplex virus (HSV) and HIV, whereas Sendai virus predominantly stimulates IFN-alpha production by monocytes. Glycosylated viral envelope proteins are known to be important for the induction of IFN-alpha. In this study we demonstrate that stimulation of IFN-alpha synthesis by HSV is inhibited by a number of monosaccharides, including fucose, N-acetylglucosamine, and N-acetylgalactosamine as well as the yeast polysaccharide mannan, supporting a role for lectin(s) in the IFN-alpha stimulation pathway. Furthermore, antiserum to the mannose receptor (MR) also inhibited HSV, vesicular stomatitis virus, and HIV-induced IFN-alpha production, but failed to inhibit the IFN-alpha induced by Sendai virus. We further demonstrated that freshly isolated blood DC and IFN-alpha-producing cells responding to HSV stimulation express the MR. This study therefore implicates the MR as an important receptor for the nonspecific recognition of enveloped viruses by DC and the subsequent stimulation of IFN-alpha production by these viruses. Thus, the MR probably serves as a critical link between innate and adaptive immunity to viruses, especially given the role of the MR in Ag capture by DC and the importance of IFN-alpha in shaping immunity.