Explore the vast range of titles available.

Premature T‐cell immunosenescence with CD57+ CD8+ T‐cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T‐cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory T cells showing increased PD1 and Eomesodermin expression. In addition, transition of naïve to CD57+ CD8+ T cells was not associated with the characteristic telomere shortening. Nevertheless, they showed the increased interferon‐gamma secretion, enhanced degranulation and reduced in vitro proliferation typical of senescent CD57+ CD8+ T cells. Thus, hyperactive PI3 kinase signaling favors premature accumulation of a CD57+ CD8+ T‐cell population, which shows most functional features of typical senescent T cells, but is different in terms of differentiation and relative telomere shortening. Initial observations indicate that this specific differentiation state may offer the opportunity to revert premature T‐cell immunosenescence and its potential contribution to inflammation and immunodeficiency in APDS. Our results show that, in APDS patients, CD57 marks a functional senescence program not strictly related to the typical phenotypic pattern and transcriptional profile of that observed in healthy adult individuals. In APDS patients, CD57 expression and functional senescence may not be associated with relative telomere shortening.

Premature T‐cell immunosenescence with CD 57 + CD 8 + T‐cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI 3 kinase delta syndrome ( APDS ). To address whether CD 57 marks the typical senescent T‐cell population seen in adult individuals or identifies a distinct population in APDS , we compared CD 57 + CD 8 + T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD 57 + CD 8 + T cells from APDS patients were less differentiated with more CD 27 + CD 28 + effector memory T cells showing increased PD 1 and Eomesodermin expression. In addition, transition of naïve to CD 57 + CD 8 + T cells was not associated with the characteristic telomere shortening. Nevertheless, they showed the increased interferon‐gamma secretion, enhanced degranulation and reduced in vitro proliferation typical of senescent CD 57 + CD 8 + T cells. Thus, hyperactive PI 3 kinase signaling favors premature accumulation of a CD 57 + CD 8 + T‐cell population, which shows most functional features of typical senescent T cells, but is different in terms of differentiation and relative telomere shortening. Initial observations indicate that this specific differentiation state may offer the opportunity to revert premature T‐cell immunosenescence and its potential contribution to inflammation and immunodeficiency in APDS .

Comparison of histone gene cluster arrangements in several species has revealed a broad spectrum of histone gene patterns. To elucidate the core histone gene organization in a mollusk, we have analyzed a Mytilus edulis genomic library and have isolated eight phage clones containing core histone genes. Analysis of insert DNA revealed that the core histone genes are arranged as regular gene repeats of all four core histones. The repeats do not contain linker histone genes. The clones are distributed into two groups of dissimilar repeated units with a common size of about 5.6 kb. The genes of each core histone class in the distinct repeats encode identical histone proteins and have comparable gene arrangements in the two repeat units. However, the intergenic sequences differ significantly. The core histone genes are organized as large clusters of about 100 repeats each. Previously, we have shown that the linker histone genes in M. edulis are also organized in a cluster of repeats of solitary H1 genes. Hence, this is the first case of a separate, clustered organization of both core and linker histone genes, respectively.