BACKGROUND: Alopecia areata (AA) is mainly a T cell-medicated autoimmune disease with non-scarring hair loss and limited treatment options. Of these, the patchy-type alopecia areata (AAP) is the most common and relatively easy to treat due to smaller areas of the scalp affected. To understand the pathogenesis of AAP and explore the therapeutic target, we focus on the molecular signatures by comparing AAP and normal subjects. METHODS: The gene expression profile (GSE68801) was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between AAP patients and normal controls using the GEO2R. Then the Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein interaction (PPI) network analysis were performed for DEGs. RESULTS: A total of 185 DEGs were identified, including 45 up-regulated genes and 140 down-regulated genes. The up-regulated DEGs were related to the immune response and chemokine signaling pathway. Meanwhile, down-regulated DEGs were enriched in keratin filament and intermediate filament. Subsequently, the top 10 hub genes were picked out in the PPI network, among them, CD2 showed the highest connectivity degree and central roles. CONCLUSION: Our data suggest that the CD2 may be a new therapeutic target for AAP. Further study is needed to explore the value of CD2 in the treatment of alopecia areata.

• MeSH
• alopecia areata genetika   terapie   MeSH
• antigeny CD2 genetika   MeSH
• genetická terapie metody   MeSH
• genetika člověka MeSH
• lidé MeSH
• stanovení celkové genové exprese metody   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Switches from the lymphoid to myeloid lineage during B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment are considered rare and thus far have been detected in MLL-rearranged leukemia. Here, we describe a novel BCP-ALL subset, switching BCP-ALL or swALL, which demonstrated monocytosis early during treatment. Despite their monocytic phenotype, 'monocytoids' share immunoreceptor gene rearrangements with leukemic B lymphoblasts. All swALLs demonstrated BCP-ALL with CD2 positivity and no MLL alterations, and the proportion of swALLs cases among BCP-ALLs was unexpectedly high (4%). The upregulation of CEBPα and demethylation of the CEBPA gene were significant in blasts at diagnosis, prior to the time when most of the switching occurs. Intermediate stages between CD14(neg)CD19(pos)CD34(pos) B lymphoblasts and CD14(pos)CD19(neg)CD34(neg) 'monocytoids' were detected, and changes in the expression of PAX5, PU1, M-CSFR, GM-CSFR and other genes accompanied the switch. Alterations in the Ikaros and ERG genes were more frequent in swALL patients; however, both were altered in only a minority of swALLs. Moreover, switching could be recapitulated in vitro and in mouse xenografts. Although children with swALL respond slowly to initial therapy, risk-based ALL therapy appears the treatment of choice for swALL. SwALL shows that transdifferentiating into monocytic lineage is specifically associated with CEBPα changes and CD2 expression.

• MeSH
• antigeny CD2 imunologie   MeSH
• buněčný rodokmen MeSH
• dítě MeSH
• imunofenotypizace MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• monocyty patologie   MeSH
• multiplexová polymerázová řetězová reakce MeSH
• pre-B-buněčná leukemie imunologie   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• reziduální nádor MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

• MeSH
• akutní lymfatická leukemie genetika   MeSH
• antigeny CD2 metabolismus   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• transkripční faktor Ikaros genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH

Porcine γδ T cells have two levels of TCRγδ expression. Whereas TCRγδ(med) cells are mostly CD2(+)CD8(-) and CD2(+)CD8(+), TCRγδ(hi) cells are highly enriched for CD2(-)CD8(-). This distribution is independent of bacterial colonization and it is already established in the thymus prior to export of γδ cells to the periphery. Sorting and cultivation experiments revealed that CD2(-)CD8(-) γδ cells are unable to acquire CD2 and CD8, whereas CD2(+) subsets can gain or loose CD8. There is also differential susceptibility for proliferation between CD2(+) and CD2(-) γδ cells. Although CD2(-)CD8(-) almost do not proliferate, proliferation of CD2(+)CD8(-) and CD2(+)CD8(+) is substantial. Population of CD2(-) γδ cells is also absent in CD1(+) immature thymocytes. Additionally, subpopulations of CD2(+) and CD2(-) γδ cells in the thymus differ in expression of auxiliary surface molecules such as CD25, CD45RA/RC, and MHC class II. Moreover, TCRγδ(hi) cells can generate TCRγδ(med) cells but never the opposite. The only exception is the thymus, where a few TCRγδ(med) cells can be induced to TCRγδ(hi) but only under IL-2 influence. The repertoire of TCRδ is polyclonal in all subsets, indicating that there is the same extent of diversification and equal capability of immune responses. Results collectively indicate that CD2 expression determines two lineages of γδ cells that differ in many aspects. Because CD2(-) γδ cells are missing in the blood of humans and mice but are obvious in other members of γδ-high species such as ruminants and birds, our findings support the idea that circulating CD2(-) γδ T cells are a specific lineage.

• MeSH
• antigeny CD1 genetika   imunologie   MeSH
• antigeny CD2 genetika   imunologie   MeSH
• antigeny CD8 genetika   imunologie   MeSH
• buněčná diferenciace imunologie   MeSH
• buněčný rodokmen imunologie   MeSH
• exprese genu MeSH
• interleukin-2 imunologie   MeSH
• lidé MeSH
• myši MeSH
• prasata MeSH
• proliferace buněk MeSH
• receptory antigenů T-buněk gama-delta genetika   imunologie   MeSH
• T-lymfocyty - podskupiny cytologie   imunologie   MeSH
• T-lymfocyty cytologie   imunologie   MeSH
• thymocyty cytologie   imunologie   MeSH
• thymus cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Developmental pathways of gammadelta T cells are still unknown, largely because of the absence of recognized lineage-specific surface markers other than the TCR. We have shown that porcine gammadelta thymocytes can be divided into 12 subsets of the following two major groups: 1) CD4(-) gammadelta thymocytes that can be further subdivided according to their CD2/CD8alphaalpha phenotype, and 2) CD4(+) gammadelta thymocytes that are always CD1(+)CD2(+)CD8alphabeta(+) and have no counterpart in the periphery. In this study, we have analyzed gammadelta thymocyte subsets with respect to behavior during cultivation, cell cycle status, and lymphocyte-specific transcripts. The group of CD4(-) gammadelta thymocytes gives rise to all gammadelta T cells found in the periphery. Proliferating CD2(+)CD8(-)CD1(+)CD45RC(-) gammadelta thymocytes are a common precursor of this group. These precursors differentiate into CD2(+)CD8alphaalpha(+), CD2(+)CD8(-), and CD2(-)CD8(-) gammadelta T cell subsets, which subsequently mature by loss of CD1 and by eventual gain of CD45RC expression. In contrast, the group of CD4(+) gammadelta thymocytes represents transient and independent subsets that are never exported from thymus as TCRgammadelta(+) T cells. In accordance with the following findings, we propose that CD4(+)CD8alphabeta(+) gammadelta thymocytes extinguish their TCRgammadelta expression and differentiate along the alphabeta T cell lineage program: 1) CD4(+) gammadelta thymocytes are actively dividing; 2) CD4(+) gammadelta thymocytes do not die, although their numbers decreased with prolonged cultivation; 3) CD4(+) gammadelta thymocytes express transcripts for RAG-1, TdT, and TCRbeta; and 4) CD4(+) gammadelta thymocytes are able to alter their phenotype to TCRalphabeta(+) thymocytes under appropriate culture conditions.

• MeSH
• antigeny CD1 metabolismus   MeSH
• antigeny CD2 metabolismus   MeSH
• antigeny CD45 imunologie   metabolismus   MeSH
• apoptóza MeSH
• buněčná diferenciace imunologie   MeSH
• buněčný rodokmen imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• fenotyp MeSH
• financování organizované MeSH
• genetická transkripce genetika   MeSH
• kultivované buňky MeSH
• pohyb buněk MeSH
• prasata imunologie   MeSH
• receptory antigenů T-buněk gama-delta genetika   imunologie   MeSH
• thymus cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• MeSH
• aktivace lymfocytů metody   MeSH
• antigeny CD2 MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitogeny MeSH
• monoklonální protilátky MeSH
• senioři MeSH
• stárnutí fyziologie   MeSH
• trypsin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH

• MeSH
• antigeny CD2 MeSH
• B-lymfocyty MeSH
• Bacteria MeSH
• Escherichia coli MeSH
• imunitní systém MeSH
• prasata MeSH
• T-lymfocyty MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• kongresy MeSH
• srovnávací studie MeSH

Východisko. V priebehu fyziologického starnutia dochádza k zmenám v imunitnom systéme na viacerých úrov- niach. Cieľom našej práce bolo porovnať schopnosť spontánnej znovuobnovy vybraných diferenciačných antigénov na lymfocytoch periférnej krvi po ich predchádzajúcej trypsinizácii v skupine zdravých osôb vyššieho a dospelého veku. Metódy a výsledky. Vyšetrili sme 24 dospelých osôb (19 - 59 rokov) a 36 starších osôb (60 - 90 rokov). Izolované lymfocyty periférnej krvi sme trypsínovali a následne inkubovali v kultivačnom médiu. Sledovali sme schopnosť spontánnej znovuobnovy diferenciačných antigénov CD2, CD4, CD8 a CD45RA. Antigén CD2 sa ani v jednej zo sledovaných skupín neobnovil na pôvodné hodnoty. Avšak rozdiel medzi jeho expresiou na lymfocytoch pred trypsínovaním a na lymfocytoch po 16-hodinovej inkubácii bol u starších osôb vyšší 16% (p < 0,001) ako v skupine dospelých osôb 7% (p < 0,01). Znovuobnova antigénu CD4 bola v oboch sledovaných skupinách skoro rovnaká. Počet CD8+ T-lymfocytov bol u starších ľudí nižší (p < 0,05), spontánna znovuobnova antigénu CD8 sa nelíšila medzi vyšetrovanými skupinami a v oboch prípadoch dosiahla východzie hodnoty. Antigén CD45RA sa u starých osôb obnovoval pomalšie, rozdiel medzi skupinami bol na hranici štatistickej významnosti (p < 0,0595). Závery. Z našich výsledkov vyplýva, že v priebehu fyziologického starnutia dochádza k zníženiu schopnosti spontánnej znovuobnovy antigénov CD2 a CD45RA, ale nie antigénov CD4 a CD8. Doposiaľ neexistuje jednoznač- né vysvetlenie prečo k tejto zmene dochádza, pravdepodobne bude podmienená viacerými faktormi. Skúmanie týchto zmien a snaha o ich ovplyvnenie môže napomôcť k pochopeniu starnutím podmienenej imunologickej dysregulácie, jej dôsledkov a prípadného terapeutického ovplyvnenia.

Background. During physiological ageing changes of the immune system take place at several levels. The objective of the submitted work was to compare the ability of spontaneous restoration of selected differentiation antigens on lymphocytes in the peripheral blood stream after previous trypsin treatment in a group of healthy elderly and adult subjects. Methods and Results. Twenty-four adults were examined (19 - 59 years) and 36 elderly subjects (60 - 90 years). Isolated lymphocytes from the peripheral blood stream were treated with trypsin and then incubated in a cultivation medium. The authors investigated the capacity of restoration of differentiation antigens CD2, CD4, CD8 and CD45RA. Antigen CD2 was not restored in any of the investigated groups to original levels. However the difference between its expression on lymphocytes before trypsin treatment and on lymphocytes after 16-hour incubation was higher in the elderly subjects 16% (p < 0.001) than in the group of adults 7% (p < 0.01). Restoration of antigen CD4 was in both investigated groups almost equal. The number of CD8+ T-lymphocytes was in elderly people lower (p < 0.05), spontaneous restoration of antigen CD8 did not differ among the investigated groups and reached in both instances the baseline value. Antigen CD45RA was restored more slowly in elderly subjects, the difference between groups was at borderline of statistical significance (p < 0.0595). Conclusion. From the results ensues that during physiological ageing the ability of spontaneous restoration of antigens CD2 and CD45RA declines but not of antigens CD4 and CD8. So far there is no unequivocal explanation why this change occurs, it is probably conditioned by several factors. Investigation of these changes and an attempt to influence them can help to understand age-conditioned immunological dysregulation, its consequences and the possibility to influence them by treatment.

• MeSH
• antigeny CD2 MeSH
• antigeny CD4 MeSH
• antigeny CD45 MeSH
• antigeny CD8 MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• stárnutí fyziologie   MeSH
• T-lymfocyty fyziologie   MeSH
• trypsin MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• antigeny CD2 metabolismus   MeSH
• podskupiny B-lymfocytů imunologie   MeSH
• prasata imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• MeSH
• antigeny CD2 analýza   MeSH
• isoantigeny analýza   MeSH
• leukocyty imunologie   MeSH
• monoklonální protilátky MeSH
• registrace MeSH