Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Langerhans cells (LC) are dendritic epidermal antigen-presenting cells expressing the surface molecule CD4, which renders them theoretical cellular targets for direct infection by the human immunodeficiency virus (HIV). To date, somewhat conflicting results have been reported concerning the in vivo infection of LC by HIV as well as the numerical alteration of these cells in the course of HIV infection. In the present work we studied clinically normal skin of a group of 44 HIV-1-seropositive patients classified according to the Centers for Disease Control (CDC) stages II (n = 14), III (n = 9), and IV (n = 21). Monoclonal antibodies (MAb) to HIV p18, p24, and gp120 and to HLA-DR and CD1a antigens (specific for LC) were applied on frozen skin sections using an amplification biotin-streptavidin-fluorescein technique. The MAb to HIV p18 cross-reacted with a cytoplasmic antigen of epidermal basal keratinocytes also present on HIV-seronegative skin specimens. No other reactivity was observed with any of the three anti-HIV MAb. The quantitative study showed that no significant correlations could be established between the number of LC (evaluated independently by HLA-DR and CD1a antigens) and the number of peripheral blood CD4+ve lymphocytes or the CDC disease stage. These results cast some doubt on the previously reported in vivo infection and numerical decrease in LC in HIV infection. The precise involvement of LC in HIV infection awaits further investigation.
 ...
PMID:Immunohistochemical study of normal skin of HIV-1-infected patients shows no evidence of infection of epidermal Langerhans cells by HIV. 247 43

In order to elucidate mucosal immunity in HIV-1 seropositive individuals, we investigated oral mucosa washings from 20 HIV-1 seropositive patients for the presence of Langerhans cells (LC) and HIV-1 antigen-positive cells, and compared the results with those obtained from 20 HIV-1 seronegative healthy individuals. Monoclonal antibodies directed against CD1a, HLA-DR, CD3, and p24 were used to identify LC, T cells and HIV-1 core-antigens, respectively. In oral mucosa washings from HIV-1 seropositive patients there was a significant reduction in the number of CD1a+ cells as compared with the healthy subjects. HIV-1 antigen-positive cells were not detected. The reduction of LC in oral mucosa washings from HIV-1 seropositive patients is probably associated with HIV-1 infection. The frequent occurrence of oral mucosal disorders in HIV-1 infected patients may in part be caused by a reduced LC-number and/or function.
 ...
PMID:Reduced number of Langerhans cells in oral mucosal washings from HIV-1 seropositives. 752 37

Langerhans cells (LC) are antigen-presenting cells which are found in areas at risk of inoculation by the human immunodeficiency virus (HIV). LC were shown to be sensitive to in vitro infection by HIV1. They could be generated in vitro by culturing CD34+ haematopoietic progenitors with GM-CSF+TNF alpha. In this study, we tested the sensitivity to HIV1 infection of in vitro generated LC throughout their differentiation and we investigated the effect of such an infection on in vitro differentiation. Phenotypic controls were performed using FACS analysis on day 6 for the presence of a CD1a+ cell population, and differentiation was assessed by transmission electron microscopy on day 13 for the presence of Birbeck granules. CD34+ cells were purified from cord blood mononuclear cells by magnetic separation. Cell suspensions were infected with either a T-lymphotropic, syncytium-inducing isolate (HXB2) or a macrophage-tropic, non-syncytium-inducing isolate (Ba-L). Viral particle release was measured by p24 antigen production in the culture supernatant. A high level of p24 production was noted on day 13 of postinfection only when infection was carried out with Ba-L isolate on cells generated after 6 days in culture with GM/CSF+TNF alpha. No infection of CD34+ progenitor cells was obtained either with Ba-L isolate or HXB2. The sensitivity of Langerhans cell/dendritic cell (LC/DC) precursors to NSI isolate (Ba-L) seemed to coincide with the early stage of differentiation (CD1a antigen appearance). The infection did not alter the differentiation of in vitro generated LC, which presented their specific ultrastructural marker of epidermal environment, i.e. Birbeck granules from day 15 of the culture as compared to control culture. These results highlight the HIV infectibility of a differentiated population of LC/DC generated in vitro from CD34+ progenitors.
 ...
PMID:In vitro HIV1 infection of CD34+ progenitor-derived dendritic/Langerhans cells at different stages of their differentiation in the presence of GM-CSF/TNF alpha. 890 26

CD1a+ dendritic cells (DC) differentiate from a major population of nonadherent CD13(hi)lin- cells that appear when human cord blood CD34+ hematopoietic progenitor cells are cultured with stem-cell factor, granulocyte/macrophage (MA) colony-stimulating factor, and tumor necrosis factor-alpha (TNF-alpha) for 5 days. CD13hilin- cells, which also comprise MA and granulocyte precursors, are CD4+ and can thus be targets of human immunodeficiency virus (HIV). Low replication was noted when these day 5 cells were infected with lymphotropic HIV-1LA1 (p24: < or = 4 ng/mL on day 8 postinfection [PI]), while high virus production occurred with MA-tropic HIV-1Ba-L, HIV-1Ada, or HIV-1-m-n. (p24: 50 to > or = 1,000 ng/mL). Strong cytopathicity (CPE) was then observed in nonadherent cells as in adherent MA. However, FACS analysis on day 7 PI showed that HIV did not affect differentiation of DC that survived CPE: apart from CD4 downmodulation related to HIV production, overall expression of CD40, CD80, and CD86 costimulatory molecules, and of HLA-DR, was unchanged relative to controls. At that time, the capacity of DC from HIV-infected cultures to stimulate the mixed leukocyte reaction was only altered less than 10-fold. Immunocytochemistry on day 7 PI showed that most HIV-infected cells were included in syncytia that were stained by anti-CD1a, anti-S100, and anti-CD14 antibodies, indicating that syncytia consisted of DC and cells of the MA lineage. Polymerase chain reaction analysis of FACS-sorted CD1a+ cells confirmed that they harbored then HIV DNA. Viral DNA was also detected in CD1a+ DC from noninfected cultures that had been exposed to HIV only after sorting. Therefore, we examined whether in infected cultures DC precursors were infected at the onset or if virus spread later from other infected cells to differentiated DC. This was answered by showing that, 24 hours postexposure to HIV, viral DNA was preferentially detected in day 5 sorted CD13hilin- versus CD13hilin- cells, and that it was found in the CD1a+ progeny of CD13(hi)lin- cells 48 hours later. In addition, HIV replication did not affect myeloid clonogenic progenitors in day 0 to day 7 PI cultures, although viral DNA was detected in colony-forming unit-granulocyte/macrophage (CFU-GM)/CFU-M colonies derived from day 3 and 7 PI cultures. Thus, precursors of DC and their progeny are susceptible to HIV in vitro, but, apart from CPE, the effect of virus production on DC differentiation or function is limited.
 ...
PMID:The effect of in vitro human immunodeficiency virus infection on dendritic-cell differentiation and function. 894 57

Lymphoid hyperplasia of Waldeyer's ring (WR) is an often-symptomatic complication of human immunodeficiency virus (HIV) infection. A characteristic but not well explained finding is the presence of multinucleated giant cells (MNGCs) adjacent to crypt or surface epithelium. To further elucidate the MNGCs and assess their relationship to HIV and Epstein-Barr virus (EBV), 12 specimens from 11 HIV-positive patients were stained with antibodies to HIV-1 p24, EBV (latent membrane protein, LMP-1), histiocytes (CD68), and other antigen-presenting cells: S-100 protein, the Langerhans cell (LC) marker CD1a, and the follicular dendritic cell (FDC) marker (CD21). Double immunofluorescent staining to assess co-expression of p24 and cell-specific markers was performed and analyzed by laser-scanning confocal microscopy with 3-dimensional reconstruction. In situ hybridization for EBV-encoded small RNA (EBER) was performed in all cases. Immunostains showed MNGCs labeled for p24, S-100, and CD68, but not CD1a. In 1 case, rare MNGCs were CD21-positive. EBV LMP-1 was uniformly negative, although EBER-positive lymphocytes were seen by in situ hybridization in 9 of 12 specimens (numerous in only 3 specimens). Double immunofluorescent staining showed co-localization of p24 with CD68 and S-100. Our results suggest that MNGCs are generally HIV-infected, EBV-negative, and most likely represent an unusual S-100-positive histiocyte subset (not LC or FDC). Their exact pathophysiologic role remains uncertain. EBV does not appear to play a major role in the pathogenesis of WR lymphoid hyperplasias in HIV infection.
 ...
PMID:HIV-associated Waldeyer's ring lymphoid hyperplasias: characterization of multinucleated giant cells and the role of Epstein-Barr virus. 1057 22

Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic infection, previously have been demonstrated to harbor significant amounts of HIV. Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs in a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by in situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found in 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68+, 3A5+, major histocompatibility complex Class II+, S-100 protein+/-, CD1a-, CD21-, CD35-, and CD83-. Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.
 ...
PMID:HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: a detailed study. 1114 25

In Thailand, the predominant HIV subtype is E, rather than Subtype B as in North America and Europe, and the predominant mode of transmission is heterosexual contact. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in vaginal mucosa of asymptomatic carriers. To examine this hypothesis, we compared vaginal tissue histology in HIV-1-seropositive cases with seronegative cases and determined the immunophenotype of HIV-1-infected cells, their numbers, and their distribution in vaginal mucosa. Vaginal biopsies were performed at four different sites from six asymptomatic HIV-1 Subtype E-infected persons and from six seronegative cases at necropsy and examined histologically. Immunophenotyping was performed using immunoperoxidase for Gag p24 HIV, CD3, CD20, CD68, CD1a, S-100 and p55 antigens and by double labeling, combining immunoperoxidase with alkaline phosphatase using pairs of the above antigens. Twenty of twenty-four vaginal biopsies (83.3%) from HIV-seropositive cases showed definite inflammation compared to five of twenty-four vaginal necropsies (20.8%) from HIV-seronegative cases. One third of HIV-seropositive biopsies (8/24) demonstrated p24-positive cells in the epithelium, whereas three-fourths (18/24) of the biopsies revealed p24-positive cells in the lamina propria. All seropositive patients showed positive cells in at least one biopsy, but not all biopsies contained positive cells. Infected cells were more frequently observed at sites of greater inflammation. The dendritic cell count in HIV-seropositive vaginal epithelium was significantly higher than that observed in the seronegative cases (P =.004). The majority of p24-positive cells in the vaginal epithelium were Langerhans cells (CD1a+/S-100+), whereas in the lamina propria, about half of p24-positive cells were Langerhans-related dendritic cells (p55+ and S-100+) and half were T lymphocytes. In conclusion, the increased propensity for heterosexual transmission of Subtype E may be related to vaginal inflammation, leading to the accumulation of Langerhans cells and related dendritic cells which, once infected with HIV, can act as a reservoir for further virus transmission.
 ...
PMID:In vivo identification of Langerhans and related dendritic cells infected with HIV-1 subtype E in vaginal mucosa of asymptomatic patients. 1174 49

Suppression of immune activation and increased inflammation are prevalent during viral infection. To investigate the role of inflammation in HIV transmission, we studied the infectious and inflammatory milieu in cervical mucosa from HIV-1- and human papillomavirus (HPV)-coinfected and HPV-monoinfected women. The numbers of cytokine-, chemokine-, and p24-expressing cells were determined using in situ imaging analysis and intracellular staining of p24 antigen. Significantly higher expression of the proinflammatory cytokines, interleukin (IL)-1alpha/beta, was seen in cervical tissue from HIV/HPV-coinfected as compared with HPV-monoinfected tissues, whereas IL-2- and interferon (IFN)-gamma-expressing cells were higher in HPV-monoinfected tissues. IL-10 was low in both groups, whereas IL-4 was significantly higher in HPV-monoinfected and HIV/HPV-coinfected tissues than in HIV/HPV-negative controls. RANTES and macrophage inflammatory protein (MIP)-1beta but not MIP-1alpha were significantly higher in the genital tract of HIV/HPV-coinfected as compared with HPV-monoinfected individuals and controls. HIV/HPV-coinfected tissues had a higher level of human leukocyte antigen D-related (HLA-DR)-expressing dendritic cells (DCs). There was a positive correlation between the number of CD4(+) and CD8(+) T cells as well as CD1a, IL-1alpha, and RANTES expression and p24 antigen-expressing cells in the HIV/HPV-coinfected tissues. These findings suggest the persistence of immune activation and inflammation in the genital tract of women with HPV monoinfection and in HIV-infected women coinfected with HPV.
 ...
PMID:Proinflammatory and type 1 cytokine expression in cervical mucosa during HIV-1 and human papillomavirus infection. 1735 67