bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of HIV transcription by CD8+ cells is mediated via multiple elements of the long terminal repeat
Authors: Maslove D M , Ni L W , Hawley-Foss N C , Badley A D , Copeland K F T 
Published: March 2003

SummaryHIV replication and LTR-mediated gene expression can be modulated by CD8+ cells in a cell type-dependent manner. We have previously shown that supernatant fluids of activated CD8+ cells of HIV-infected individuals suppress long terminal repeat (LTR)-mediated transcription of HIV in T cells while enhancing transcription in monocytic cells. Here, we have examined the effect of culture of T cells and monocytic cells with CD8+ supernatant fluids, and subsequent binding of transcription factors to the HIV-1 LTR. In transfections using constructs in which NFκB or NFAT-1 sites were mutated, the LTR retained the ability to respond positively to culture with CD8 supernatant fluid in monocytic cells. Nuclear extracts prepared from both Jurkat T cells and U38 monocytic cells cultured with CD8+ cell supernatant fluid demonstrated increased binding to the HIV-1 LTR at an AP-1 site which overlapped the chicken ovalbumin upstream promoter (COUP) site. In monocytic cells, increased binding activity was observed at the NFκB sites of the LTR. In contrast, an inhibition in binding at the NFκB sites was observed in Jurkat cells. Examination of two NFAT-1 sites revealed enhanced binding at − 260 to − 275 bp in U38 cells which was reduced by cellular activation. PMA and ionomycin-induced binding at a second NFAT-1 site (− 205 to − 216 bp) was abrogated by CD8+ cell supernatant fluid in T cells. These results, taken together, suggest that factors present in CD8+ supernatant fluids may act through several sites of the LTR to modulate transcription in a cell type-dependant manner.
HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus
Authors: Viallard J F , Bloch-Michel C , Neau-Cransac M , Taupin J L , Garrigue S , Miossec V , Mercie P , Pellegrin J L , Moreau J F 
Published: March 2003

Summary
A major problem in the management of SLE patients is to predict a flare or to distinguish between active and quiescent disease. Serological markers are widely used to assess disease activity, but many patients have close to or normal values for these parameters while exhibiting obvious disease-related signs and symptoms. This study aimed to determine which serological parameters, among ESR, ANA and anti-dsDNA antibody titres, CH50 and the HLA-DR expression on circulating T-lymphocyte subsets, best reflected the development of SLE flares. Sixty SLE patients were included, 34 with quiescent disease throughout the entire follow-up period and 26 who experienced an SLE flare defined as having active disease. According to univariate analysis, all parameters were significantly higher for patients with active disease, with the percentage of CD8+DR+ cells being the most significant parameter (P = 10−7). Multivariate logistic regression analysis identified three independent variables enabling the identification of a lupus flare: CH50, the CD8+DR+ and CD4+DR+ cell percentages among total lymphocytes. The CD8+DR+ cell percentage is the biological parameter most significantly associated with a flare (P &lt; 0·001), even more powerful than CH50 (P &lt; 0·01). HLA-DR expression on CD8+ lymphocytes clearly coincided with disease evolution in seven patients enrolled as having quiescent disease, but who experienced one flare during follow-up that subsequently resolved. The percentage of circulating CD8+DR+ lymphocytes appears to be a biological marker which accurately reflects disease activity. A larger prospective study is needed to demonstrate the real efficacy of this marker in predicting an exacerbation in SLE patients.
Effects of vitamin D on the growth of normal and malignant B-cell progenitors
Authors: Consolini R , Pala S , Legitimo A , Crimaldi G , Ferrari S , Ferrari S 
Published: March 2003

SummaryAs the effects of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) (VD, calcitriol) on the proliferation and differentiation potential of normal and leukaemic cells in vitro of myeloid lineage are known, we investigated the response to VD on the growth of both normal and malignant lymphoid progenitors. Effects of vitamin D on normal human lymphoid progenitors and B lineage acute lymphoblastic leukaemia (ALL) progenitors were assessed by using an in vitro cell colony assay specific for either B or T cell lineages. The expression of VDR on B untreated malignant progenitors at diagnosis was investigated by RT-PCR analysis. VD induced a significant inhibition of normal lymphoid cell progenitors growth of both T and B lineage. VD inhibited significantly also the growth of malignant B cell lineage lymphoid progenitors, without inducing cytotoxic effect. As it has been reported that VD effects on activated lymphocytes are mediated by 1,25-(OH)2-D3 nuclear receptor (VDR), we investigated VDR expression on malignant B cell progenitors. We did not detect VDR expression on these cells examined at diagnosis. We demonstrated that VD inhibited in vitro the clonogenic growth of both normal and malignant lymphoid B cell progenitors and that this inhibitory effect on malignant B cell progenitors was not related to VDR. Our work contributes to understanding of the mechanism of action of this hormone in promoting cellular inhibition of clonal growth of malignant lymphoid B cell progenitors, suggesting that the regulation of some critical growth and differentiation factor receptors could be a key physiological role of this hormone.
Influence of atopic heredity on IL-4-, IL-12- and IFN-γ-producing cells inin vitroactivated cord blood mononuclear cells
Authors: Gabrielsson S , Söderlund A , Nilsson C , Lilja G , Nordlund M , Troye-Blomberg M 
Published: March 2003

SummarySeveral reports have claimed that there is a greater risk for a child with an atopic mother to develop allergy as compared to a child with an atopic father. This suggests that the fetal environment during pregnancy might be of importance for the development of atopic disease. Both proliferative and cytokine responses have been detected in cord blood mononuclear cells (CBMC) after stimulation with allergens, suggesting allergen priming already in utero. The aim of this study was to investigate whether the atopic status of the mother influences cytokine production by CBMC. We compared interleukin (IL)-4, IL-12 and interferon (IFN)-γ-producing CBMC from children with double atopic heredity (dh), maternal atopic heredity only (mh) or no atopic heredity (nh). CBMC were stimulated in vitro with allergens (birch, ovalbumin and cat), phytohaemagglutinin (PHA) or purified protein derivative (PPD) and cytokine-producing cells were measured by the enzyme-linked immunospot assay. In response to PHA, the frequency of IL-4-producing cells, as well as the ratio of IL-4/IFN-γ-producing cells, were significantly higher in the dh group compared to the nh group. High numbers of IL-12-producing cells in response to allergens were detected, significantly highest in the nh group, followed by the dh and mh groups. Our results suggest that there is a stronger Th2 bias after in vitro stimulation of CBMC from children with atopic heredity, as reflected by higher IL-4/IFN-γ ratios in response to PHA, and lower numbers of IL-12-producing cells after allergen stimulation. Whether these differences influence later allergy development will be evaluated when the atopic status of the children is assessed at 2 years of age.
Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis
Authors: KAKINUMA T , NAKAMURA K , WAKUGAWA M , MITSUI H , TADA Y , SAEKI H , TORII H , KOMINE M , ASAHINA A , TAMAKI K 
Published: March 2003

SummaryAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage-derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E-selectin levels, serum soluble interleukin-2 receptor (sIL-2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD.
Lidocaine inhibits secretion of IL-8 and IL-1βand stimulates secretion of IL-1 receptor antagonist by epithelial cells
Authors: LAHAV M , LEVITE M , BASSANI L , LANG A , FIDDER H , TAL R , BAR-MEIR S , MAYER L , CHOWERS Y 
Published: March 2003

SummaryLidocaine and related local anaesthetics have been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms underlying their therapeutic effect are poorly defined. Intestinal epithelial cells play an important role in the mucosal inflammatory response that leads to tissue damage in UC via the secretion of pro-inflammatory cytokines and chemokines. The aim of this study was to evaluate the direct immunoregulatory effect of lidocaine on pro-inflammatory cytokine and chemokine secretion from intestinal epithelial cells. HT-29 and Caco-2 cell lines were used as a model system and treated with lidocaine and related drugs. The expression of IL-8, IL-1β and the IL-1 receptor antagonist (RA) were assessed by ELISA and quantification of mRNA. In further experiments, the effect of lidocaine on the secretion of IL-8 from freshly isolated epithelial cells stimulated with TNFα was tested. Lidocaine, in therapeutic concentrations, inhibited the spontaneous and TNFα-stimulated secretion of IL-8 and IL-1β from HT-29 and Caco-2 cell lines in a dose-dependent manner. Similarly, suppression of IL-8 secretion was noted in the freshly isolated epithelial cells. Other local anaesthetics, bupivacaine and amethocaine, had comparable effects. Lidocaine stimulated the secretion of the anti-inflammatory molecule IL-1 RA. Both the inhibitory and the stimulatory effects of lidocaine involved regulation of transcription. The results imply that the therapeutic effect of lidocaine may be mediated, at least in part, by its direct effects on epithelial cells to inhibit the secretion of proinflammatory molecules on one hand while triggering the secretion of anti-inflammatory mediators on the other.
Adhesion to fibronectin viaα4 integrin (CD49d) protects B cells from apoptosis induced by serum deprivation but not via IgM or Fas/Apo-1 receptors
Authors: GARCIA-GILA M , LÓPEZ-MARTIN E M , GARCIA-PARDO A 
Published: March 2003

SUMMARYApoptosis is a regulated event crucial to the development and proliferation of normal and malignant B cells. We have studied the role of signals delivered via α4 integrin on apoptosis triggered by three different pathways on these cells. For apoptosis induced by serum deprivation, culturing B cells on the recombinant fibronectin fragment H89, a known ligand for α4β1 integrin, resulted in statistically significant (P &lt; 0·005) higher viability values (68%, 65% and 67%) for Ramos, Nalm-6 and EHEB cells, respectively, than culturing cells on poly lysine (42%, 42% and 48%). An antiα4 MoAb reverted the protecting effect, thus confirming that it was due specifically to α4 engagement. Similarly, cells cultured on FN-III4-5, a recently identified fibronectin region which binds activated α4 integrin, also showed statistically significant higher viability than poly lysine cultures. α4 engagement however, did not prevent apoptosis induced on Ramos cells via surface IgM. Adhesion of IM-9 cells, a myeloma cell line carrying functional Fas receptors, to the H89 fragment neither increased cell viability upon triggering apoptosis via Fas when compared to poly lysine. These results indicate that α4 signalling may overcome B cell apoptosis induced by the lack of growth factors but does not seem to affect the IgM or Fas apoptotic pathways, thus suggesting different intracellular mechanisms for these processes.
Age-related differences in cell-specific cytokine production by acutely ill Malawian patients
Authors: PETTIFORD J N , JASON J , NWANYANWU O C , ARCHIBALD L K , KAZEMBE P N , DOBBIE H , JARVIS W R 
Published: March 2003

SUMMARYAge-related changes in human cell-specific cytokine responses to acute illness have not been well examined. We therefore evaluated age-related differences in T, B and natural killer (NK) peripheral blood lymphocyte cytokine responses of 309 acutely ill hospitalized people in Malawi, Africa, &lt;1 month–61 years of age. We used four-colour flow cytometry and performed Wilcoxon rank sum and Kruskal–Wallis tests, Pearson (rp) and Spearman (rs) correlations, and linear and logistic regression analyses to control for human immunodeficiency virus infection (HIV) status, the percentages of lymphocytes expressing CD4, and the nature of the acute infection. The percentages of CD8− and CD8+ T cells producing induced IL-8 decreased with age (rs = −0·44 and −0·53). The percentages of T cells producing TNF-α were higher, and the percentages producing IL-10 were lower, in those ≥13 than those &lt;13 years old (medians: 17·7 versus 10·5 and 1·4 versus 3·0, respectively). The percentages of CD8− T cells producing IFN-γ were higher and stable in those ≥1 year old compared to infants (medians: 23·5 versus 10·4); the percentages of NK producing IFN-γ were higher post-infancy and then declined to relatively low levels with increasing age. The percentages of T cells producing IL-2 were highest in those 5–&lt;31 years old (median 5·6) and lowest in those ≥31 years old (median 1·9). The ratios of the percentages of T cells producing IL-4 to those producing IL-8 and to those producing IL-10 both increased with age. These data suggest that innate immunity, represented by NK IFN-γ production, dominates in early life. A number of shifts occur after infancy and before adolescence, including a proinflammatory shift from IL-8 to TNF-γ and a type 2 shift from IL-10 to IL-4 dominance. These findings suggest distinct age-related differences in the human response to acute illness and may be useful in directing future efforts at immunomodulatory therapies.
Neonatal dendritic cells are intrinsically biased against Th-1 immune responses
Authors: LANGRISH C L , BUDDLE J C , THRASHER A J , GOLDBLATT D 
Published: March 2003

SUMMARYDendritic cells (DCs) were derived from human peripheral blood monocytes or cord blood monocytes cultured in the presence of IL-4 and GM-CSF. Adult and cord DCs were observed to have comparable immature phenotypes. However, the increase in surface expression of HLA-DR and CD86 after addition of LPS was significantly attenuated in cord DCs, with CD25 and CD83 expression also markedly reduced. Cord DCs were also unable to produce IL-12p70, failed to down-regulate expression of the chemokine receptor CCR5 and induced lower levels of IFN-γ production from allogeneic naive CD4+ T cells than their adult counterparts. In contrast, the kinetics of the production of TNF-α and IL-10 in response to LPS stimulation was comparable to adult DCs. The reduced ability of cord DCs to attain a fully mature adult phenotype, and to activate naive CD4+ T cells to produce IFN-γ, suggests that they are intrinsically preprogrammed against the generation of Th-1 immune responses.
A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza
Authors: NABESHIMA S , MURATA M , KIKUCHI K , IKEMATSU H , KASHIWAGI S , HAYASHI J 
Published: March 2003

SUMMARYInfluenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-γ production in the acute (days 1–3) and recovery phases (days 9–12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28− CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO− subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-γ in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-γ−/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.
Immunological and pathological comparative analysis between experimental latent tuberculous infection and progressive pulmonary tuberculosis
Authors: ARRIAGA A K , OROZCO E H , AGUILAR L D , ROOK G A W , PANDO R HERNÁNDEZ 
Published: March 2003

SUMMARYMycobacterium tuberculosis produces latent infection or progressive disease. Indeed, latent infection is more common since it occurs in one-third of the world's population. We showed previously, using human material with latent tuberculosis, that mycobacterial DNA can be detected by in situ PCR in a variety of cell types in histologically-normal lung. We therefore sought to establish an experimental model in which this phenomenon could be studied in detail. We report here the establishment of such a model in C57Bl/6 × DBA/2 F1 hybrid mice by the intratracheal injection of low numbers of virulent mycobacteria (4000). Latent infection was characterized by low and stable bacillary counts without death of animals. Histological and immunological study showed granulomas and small patches of alveolitis, with high expression of tumour necrosis factor alpha (TNFα), inducible nitiric oxide synthase (iNOS), interleukin 2 (IL-2) and interferon gamma (IFNγ). In contrast, the intratracheal instillation of high numbers of bacteria (1 × 106) produced progressive disease. These animals started to die after 2 months of infection, with very high bacillary loads, massive pneumonia, falling expression of TNF-α and iNOS, and a mixed Th1/Th2 cytokine pattern. In situ PCR to detect mycobacterial DNA revealed that the most common positive cells in latently-infected mice were alveolar and interstitial macrophages located in tuberculous lesions, but, as in latently-infected human lung, positive signals were also seen in bronchial epithelium, endothelial cells and fibroblasts from histologically-normal areas. Our results suggest that latent tuberculosis is induced and maintained by a type 1 cytokine pattern plus TNFα, and that mycobacteria persist intracellularly in lung tissue with and without histological evidence of a local immune response.
Profiles of IFN-γand its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis
Authors: LEE J -S , SONG C -H , KIM C -H , KONG S -J , SHON M -H , KIM H -J , PARK J -K , PAIK T -H , JO E -K 
Published: March 2003

SUMMARYThis study investigated the profiles of IFN-γ and its regulatory cytokines (IL-12, IL-18 and IL-10) in response to a purified protein derivative (PPD) antigen in peripheral blood mononuclear cells (PBMC) from 18 HIV-negative patients with multidrug-resistant tuberculosis (MDRTB), and compared them with those from 19 healthy tuberculin reactors (HTR). ELISA results showed that following stimulation with PPD, IFN-γ production was significantly reduced, whereas production of both IL-18 and IL-10 was significantly elevated in MDRTB patients compared with HTR. Three out of 18 patients with MDRTB of greater than 4 years duration showed significantly elevated IL-12 p70 production, induced by in vitro PPD stimulation of their PBMC, when compared with data from HTR. However, when taken as a group, MDRTB patients were similar to HTR in their IL-12 p70-producing capacity. IL-12 p70 protein paralleled IL-12 p40 protein expression. In addition, the production of IL-12 p40 was significantly correlated with IL-10 in all patients, but was not correlated with IFN-γ. Neutralization of IL-10 increased IL-12 p40 about twofold, but did not significantly alter IFN-γ induction in MDRTB. IFN-γ in MDRTB was highly correlated with lymphoproliferation and CD4 counts, but was not correlated with IL-12, IL-18 or IL-10 production. Our findings suggest that patients with MDRTB have dysregulated IL-12, IL-18 and IL-10 production during Mycobacterium tuberculosis infection, and the cytokine profiles are similar to those in patients with drug-sensitive advanced TB previously reported in the literature. In addition, IL-10 may not have a dominant role in defective IFN-γ production in patients with MDRTB.
The transcriptional response of human macrophages to murabutide reflects a spectrum of biological effects for the synthetic immunomodulator
Authors: GOASDUFF T , DARCISSAC E C A , VIDAL V , CAPRON A , BAHR G M 
Published: March 2003

SUMMARY
The synthetic immunomodulator murabutide (MB) presents multiple biological activities with minimal toxicity in animals and in man. Although MB is known to target cells of the reticuloendothelial system and to regulate cytokine synthesis, the molecular mechanisms underlying several of its biological effects are still largely unknown. In an effort to define cellular factors implicated in the immunomodulatory and HIV-suppressive activities of MB, we have undertaken profiling the regulated expression of genes in human monocyte-derived macrophages (MDM) following a 6-h stimulation with this synthetic glycopeptide. Oligonucleotide microarray analysis was performed on RNA samples of differentiated MDM from four separate donors, using probe sets corresponding to 1081 genes. We have identified, in a reproducible fashion, the enhanced expression of 40 genes and the inhibition of 16 others in MB-treated MDM. These regulated genes belonged to different families of immune mediators or their receptors, transcription factors and kinases, matrix proteins and their inhibitors, ion channels and transporters, and proteins involved in cell metabolic pathways. Additional verification of the regulated expression of selected genes was carried out using Northern blots or the quantification of released proteins in MDM cultures. The profile of MB-regulated genes in MDM provides a molecular basis for some of its previously reported biological activities, and reveals new set of genes targeted by the immunomodulator suggesting potential application in novel therapeutic indications.