Severe herpes virus (HSV-2) infection in two patients with myelodysplasia and undetectable NK cells and plasmacytoid dendritic cells in the blood.
Journal - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology (Netherlands )
BACKGROUND: How the immune system contains herpes simplex virus (HSV) infections is partly understood. T cells from infected persons proliferate in response to HSV antigens in vitro and may control local relapse rather than primary infection. NK cells have been involved in the control of experimental infections. A potentially important, as yet unexplored, population of interest might be the plasmacytoid dendritic cells (PDC), which contrary to monocytes, produce very high amounts of the major antiviral molecules, type-I interferon (IFN) following interaction with HSV. OBJECTIVES: Measure type-I IFN production, PDC, and NK cells in patients with unusually severe HSV infections. STUDY DESIGN: Two female patients of 33- and 50-year-old, respectively were referred because of severe disseminated HSV2 infection and myelodysplastic marrow. One patient had leukaemia and a primary HSV2 infection whereas the other had systemic lupus erythematosus (SLE) and a chronic HSV2 infection. The following studies were performed at various time points over 18 months: analysis of the lymphocytes and PDC subsets phenotype, lymphocyte proliferation assays to recall antigens; generation of NK cells in cultures, and production of type-I IFN in serum and by HSV-infected and by sendai virus (SV)-infected blood cells. RESULTS AND CONCLUSIONS: PDC and NK cells were undetectable in the blood of both patients and NK cells could not be generated in culture at the time of ongoing infection. PBMC failed to produce IFN after infection with HSV contrasting with a normal T cell proliferation to HSV antigens in patient 1. Our observation suggests that innate immunity, through NK cells and PDC may control HSV infections, and together with IFN-producing capacity, should be investigated in patients with unusually severe HSV infections.
|ISSN : ||1386-6532|
|Mesh Heading : ||Adult Dendritic Cells Female Herpes Simplex Herpesvirus 2, Human Humans Immunophenotyping Interferon Type I Killer Cells, Natural Lymphocyte Activation Middle Aged Myelodysplastic Syndromes immunology physiopathology virology metabolism immunology|
|Mesh Heading Relevant : ||pathology immunology pathology complications|
Functional and phenotypic analysis of thymic CD34+CD1a- progenitor-derived dendritic cells: predominance of CD1a+ differentiation pathway.
Journal - Journal of immunology (Baltimore, Md. : 1950) (UNITED STATES )
Whether thymic dendritic cells (DC) are phenotypically and functionally distinct from the monocyte lineage DC is an important question. Human thymic progenitors differentiate into T, NK, and DC. The latter induce clonal deletion of autoreactive thymocytes and therefore might be different from their monocyte-derived counterparts. The cytokines needed for the differentiation of DC from thymic progenitors were also questioned, particularly the need for GM-CSF. We show that various cytokine combinations with or without GM-CSF generated DC from CD34+CD1a- but not from CD34+CD1a+ thymocytes. CD34+ thymic cells generated far fewer DC than their counterparts from the cord blood. The requirement for IL-7 was strict whereas GM-CSF was dispensable but nonetheless improved the yield of DC. CD14+ monocytic intermediates were not detected in these cultures unless macrophage-CSF (M-CSF) was added. Cultures in M-CSF generated CD14-CD1a+ DC precursors but also CD14+CD1a- cells. When sorted and recultured in GM-CSF, CD14+ cells down-regulated CD14 and up-regulated CD1a. TNF-alpha accelerated the differentiation of progenitors into DC and augmented MHC class II transport to the membrane, resulting in improved capacity to induce MLR. The trafficking of MHC class II molecules was studied by metabolic labeling and immunoprecipitation. MHC class II molecules were transported to the membrane in association with invariant chain isoforms in CD14+ (monocyte)-derived and in CD1a+ thymic-derived DC but not in monocytes. Thus, thymic progenitors can differentiate into DC along a preferential CD1a+ pathway but have conserved a CD14+ maturation capacity under M-CSF. Finally, CD1a+-derived thymic DC and monocyte-derived DC share very close Ag-processing machinery.
|ISSN : ||0022-1767|
|Mesh Heading : ||Antigens, CD Antigens, CD1 Antigens, CD14 Antigens, CD34 Cell Differentiation Child Dendritic Cells Granulocyte-Macrophage Colony-Stimulating Factor Histocompatibility Antigens Class II Humans Macrophage Colony-Stimulating Factor Monocytes Phenotype Stem Cells Thymus Gland Tumor Necrosis Factor-alpha isolation & purification isolation & purification immunology pharmacology isolation & purification pharmacology cytology immunology drug effects immunology drug effects immunology pharmacology|
|Mesh Heading Relevant : ||isolation & purification isolation & purification cytology cytology cytology|
Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.
Journal - The Journal of clinical investigation (UNITED STATES )
Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production.
|ISSN : ||0021-9738|
|Mesh Heading : ||Antibodies, Monoclonal Basophils Cells, Cultured Female Humans Interleukin-3 Keratinocytes RNA, Messenger Receptors, IgE immunology genetics analysis genetics|
|Mesh Heading Relevant : ||physiology physiology physiology physiology|