Biomedical subjects

Eva Jiménez

Publications and source records attributed to Eva Jiménez.

10 recordsLinked to original sources

PubMed2006

Thymic alterations in EphA4-deficient mice.

In the present work, we have demonstrated in vivo an altered maturation of the thymic epithelium that results in defective T cell development which increases with age, in the thymus of Eph A4-deficient mice. The deficient thymi are hypocellular and show decreased proportions of double-positive (CD4+CD8+) cells which reach minimal numbers in 4-wk-old thymi. The EphA4 (-/-) phenotype correlates with an early block of T cell precursor differentiation that results in accumulation of CD44-CD25+ triple-negative cells and, sometimes, of CD44+CD25- triple-negative thymocytes as well as with increased numbers of apoptotic cells and an important reduction in the numbers of cycling thymocytes. Various approaches support a key role of the thymic epithelial cells in the observed phenotype. Thymic cytoarchitecture undergoes profound changes earlier than those found in the thymocyte maturation. Thymic cortex is extremely reduced and consists of densely packed thymic epithelial cells. Presumably the lack of forward Eph A4 signaling in the Eph A4 -/- epithelial cells affects their development and finally results in altered T cell development.

Animals↗

PubMed2004

Prolactin affects both survival and differentiation of T-cell progenitors.

We have analysed the in vitro effects of prolactin on thymocyte development concluding that PRL favours the survival and differentiation of T-cell progenitors. Fetal, adult thymocytes and CD45(+) fetal liver lymphoid progenitors express PRL-R. PRL induces survival, proliferation and differentiation of lymphoid progenitors whereas both an anti-PRL antiserum and an anti-PRL-R mAb block T-cell development accumulating CD25(+)DN (CD4(-)CD8(-)) cells. Furthermore, IL2 rescues the blockade of T-cell development in FTOC treated with anti-PRL antiserum but PRL does not recover cultures treated with an anti-IL2R alpha chain mAb, which drastically blocks the T-cell development. These results support IL2/IL2R mediation of PRL effects on developing thymocytes.

Animals↗

PubMed2004

Identification of the protein components of protein-bound polysaccharide (PSK) that interact with NKL cells.

We identified the protein components of a protein-bound polysaccharide (PSK) that are responsible for the biological function of this immunomodulator in its interaction with NKL cells, an NK-derived cell line previously known to be activated by this extract, obtained from the basidiomycete Coriolus versiocolor. In addition, we show that PSK protein interacts with NKL cells through a different receptor from that used by IL-2. This was deduced from the different molecular weights of the PSK/NKL and IL-2/NKL receptor complexes. We show that PSK is composed of a highly glycosylated 12-kDa protein. Protein-bound polysaccharide interacts in vitro with an NKL receptor of approximately 48 kDa, whereas IL-2 shows a similar interaction with NKL receptor proteins of approximately 64 and 75 kDa. Our results may explain why PSK and IL-2 use completely different intracellular routes for their biological activities in NKL cells-i.e., regulating different PKC isozymes, mitogen-activated protein kinases, and nuclear transcription factors.

Antineoplastic Agents↗

PubMed2004

Prolactin stimulates maturation and function of rat thymic dendritic cells.

The current study analyses the effect of PRL, a hormone involved in numerous physiological processes, on dendritic cells (DC) of rat thymus. Most thymic DC express prolactin receptors (PRL-R) as demonstrated by both immunohistochemistry and flow cytometry. PRL administration during 2 or 6 days to fetal thymus organ cultures (FTOC) does not increase the proportions of DC in cultures but stimulates their differentiation. Furthermore, PRL-treated thymic DC exhibit increased allostimulatory capacity in mixed leukocyte reaction (MLR) assays in association with increased surface expression of both MHC antigens and the co-stimulatory molecule CD80. PRL-treated DC also produce increased amounts of pro-inflammatory cytokines, such as IL-12, TNFalpha and IL-1beta, but not of IL6 or IL-10. Our data suggest a key role for IL-12 in the observed changes in the allostimulatory capacity of PRL-treated DC. Also, they permit us to hypothesize about the physiological role played by PRL in thymus ontogeny.

Animals↗

PubMed2003

Age-dependent changes in thymic macrophages and dendritic cells.

Aging is characterized by the decline and deregulation of several physiological systems, especially the immune system. The involution of the thymus gland has been identified as one of the key events that precedes the age-related decline in immune function. Whereas the decrease in thymocyte numbers and in the thymic output during thymus atrophy has been analyzed by various authors, very little information is available about the age-associated modifications in thymic macrophages and dendritic cells. Here we present evidence that these thymic stromal cell components are only slightly affected by age.

Aging↗

PubMed2002

Expression and function of the Eph A receptors and their ligands ephrins A in the rat thymus.

Thymus development and function are dependent on the definition of different and graded microenvironments that provide the maturing T cell with the different signals that drive its maturation to a functional T lymphocyte. In these processes, cell-cell interactions, cell migration, and positioning are clues for the correct functioning of the organ. The Eph family of receptor tyrosine kinases and their ligands, the ephrins, has been implicated in all these processes by regulating cytoskeleton and adhesion functioning, but a systemic analysis of their presence and possible functional role in thymus has not yet been conducted. In this regard, the current study combines different experimental approaches for analyzing the expression of four members of the Eph A family and their ligands, ephrins A, in the embryonic and adult rat thymus. The patterns of Eph and ephrin expression in the distinct thymic regions were different but overlapping. In general, the studied Eph A were expressed on thymic epithelial cells, whereas ephrins A seem to be more restricted to thymocytes, although Eph A1 and ephrin A1 are expressed on both cell types. Furthermore, the supply of either Eph A-Fc or ephrin A-Fc fusion proteins to fetal thymus organ cultures interferes with T cell development, suggesting an important role for this family of proteins in the cell mechanisms that drive intrathymic T cell development.

Animals↗

PubMed2002

Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus-derived cells that undergo post-thymic maturation to become functionally mature CD4+ T lymphocytes.

CD4+CD8+ double-positive (DP) T cells represent a minor subpopulation of T lymphocytes found in the periphery of adult rats. In this study, we show that peripheral DP T cells appear among the first T cells that colonize the peripheral lymphoid organs during fetal life, and represent approximately 40% of peripheral T cells during the perinatal period. Later their proportion decreases to reach the low values seen in adulthood. Most DP T cells are small size lymphocytes that do not exhibit an activated phenotype, and their proliferative rate is similar to that of the other peripheral T cell subpopulations. Only 30-40% of DP T cells expresses CD8beta chain, the remaining cells expressing CD8alphaalpha homodimers. However, both DP T cell subsets have an intrathymic origin since they appear in the recent thymic emigrant population after injection of FITC intrathymically. Functionally, although DP T cells are resistant to undergo apoptosis in response to glucocorticoids, they show poor proliferative responses upon CD3/TCR stimulation due to their inability to produce IL-2. A fraction of DP T cells are not actively synthesizing the CD8 coreceptor, and they gradually differentiate to the CD4 cell lineage in reaggregation cultures. Transfer of DP T lymphocytes into thymectomized SCID mice demonstrates that these cells undergo post-thymic maturation in the peripheral lymphoid organs and that their CD4 cell progeny is fully immunocompetent, as judged by its ability to survive and expand in peripheral lymphoid organs, to proliferate in response to CD3 ligation, and to produce IL-2 upon stimulation.

Aging↗

PubMed2002

Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development.

The present study investigated the potential role of stromal cell-derived factor 1 (SDF-1) in human intrathymic T-cell differentiation. Results show that SDF-1 is produced by human thymic epithelial cells from the subcapsular and medullary areas, and its receptor, CXCR4, is up-regulated on CD34(+) precursor cells committed to the T-cell lineage. Chimeric human-mouse fetal thymus organ culture (FTOC) seeded with purified CD34(+) thymic progenitors and treated with neutralizing antibodies against SDF-1 or CXCR4 showed a significant reduction of the number of human thymocytes and an arrested thymocyte differentiation in the transition between CD34(+) precursor cells and CD4(+) immature thymocytes. SDF-1-treated FTOC showed an increase of human thymocyte numbers, mainly affecting the most immature subpopulations. Moreover, these results suggest that CXCR4/SDF-1 signaling is not critical for the CD34(+) cell precursor recruitment to the thymus. On the other hand, SDF-1 significantly increased the viability of CD34(+) T-cell precursors modulating the expression of BCL-2 and BAX genes, and stimulated the proliferation of CD34(+) thymic precursor cells, particularly in synergy with interleukin 7 (IL-7), but not with other cytokines, such as stem cell factor or flt3-ligand. Accordingly, only IL-7 was able to up-regulate CXCR4 expression on CD34(+) thymic progenitors. In addition, deprivation of SDF-1 partially inhibited human thymocyte expansion induced by IL-7 in human-mouse FTOC. This study indicates that SDF-1/CXCR4 signaling is required for the survival, expansion, and subsequent differentiation of human early thymocytes and identifies a new mechanism by which IL-7 mediates its effects on human thymopoiesis.

Animals↗

PubMedDate not supplied

Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution?

The 22 nucleotide let-7 small temporal RNA has been found consistently in samples from diverse bilateria but not from sponge or cnidarians. Here we further examine the phylogenetic distribution of this regulatory RNA by sampling representatives of diverse metazoan lineages. The 22 nucleotide let-7 RNA is detectable in triclad and polyclad platyhelminths, nemertean, and chaetognath but not ctenophore or acoel metazoans. These results support recent arguments that acoels are distinct from other acoelomate platyhelminths. We argue that let-7 is not a bilaterian or triploblast synapomorphy but instead evolved later in metazoan evolution, perhaps in association with complex life history traits.

Animals↗

PubMedDate not supplied

The Hox gene complement of acoel flatworms, a basal bilaterian clade.

Several molecular data sets suggest that acoelomorph flatworms are not members of the phylum Platyhelminthes but form a separate branch of the Metazoa that diverged from all other bilaterian animals before the separation of protostomes and deuterostomes. Here we examine the Hox gene complement of the acoel flatworms. In two distantly related acoel taxa, we identify only three distinct classes of Hox gene: an anterior gene, a posterior gene, and a central class gene most similar to genes of Hox classes 4 and 5 in other Bilateria. Phylogenetic analysis of these genes, together with the acoel caudal homologue, supports the basal position of the acoels. The similar gene sets found in two distantly related acoels suggest that this reduced gene complement may be ancestral in the acoels and that the acoels may have diverged from other bilaterians before elaboration of the 8- to 10-gene Hox cluster that characterizes most bilaterians.

Amino Acid Sequence↗