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Biomedical subjects

Ana Cumano

Publications and source records attributed to Ana Cumano.

7 recordsLinked to original sources
PubMed2003

Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development.

Deletions of interleukin 7 (IL-7) or its receptor components permit fetal but not adult B cell development in mice. Mice deficient in IL-7 receptor alpha (IL-7R alpha) had 1% the number of B cells of controls and 10% that of mice deficient in the common gamma chain. As IL-7R alpha is also a receptor for thymic stromal-derived lymphopoietin (TSLP), we assayed the ability of TSLP to support proliferation of fetal or adult precursor B cells. Only fetal-derived pro-B cells were able to respond to TSLP, although pre-B cells from both origins were TSLP-responsive. Fetal but not adult precursors generated a measurable B cell compartment in the absence of IL-7. The residual B cells found in IL-7R alpha-deficient mice required fetal liver kinase 2 (Flk-2) for their development. Thus, IL-7R alpha- and Flk-2-mediated signals account for the generation of almost all mouse B lymphocytes.

Animals↗
PubMed2003

Monoallelic expression of the murine gene encoding Toll-like receptor 4.

Defects in the gene encoding Toll-like receptor 4 (Tlr4) result in impaired responses to lipopolysaccharide (LPS), rendering mice sensitive to infections by Gram-negative bacteria. C3H/HeJ mice have a codominant allele with a mutation in Tlr4, which results in an intermediate response to LPS in F1 mice from crosses of responder and C3H/HeJ mice. Here we show that this intermediate response to LPS is due to monoallelic expression of Tlr4. Allele usage is maintained during clonal expansion, a situation that resembles allelic exclusion. In contrast, Tlr4 is deleted on the recessive C57BL/10ScCr allele and all cells from F1 mice from crosses of responder and C57BL/10ScCr mice express TLR4 protein. Thus, Tlr4 is an autosomal gene whose expression is regulated similarly to that of genes on the X chromosome.

Alleles↗
PubMed2003

The repertoires of circulating human CD8(+) central and effector memory T cell subsets are largely distinct.

Memory T cells are divided into central and effector subsets with distinct functions and homing capabilities. We analyzed the composition and dynamics of the CD8(+) T cell repertoire of these subsets within the peripheral blood of four healthy individuals. Both subsets had largely distinct and autonomous TCRbeta repertoires. Their composition remained stable over a 9 month period, during which no cell passage between these subsets was detected despite important size variation of several clones. In one donor, four out of six TCRbeta clonotypes specific for the influenza A virus were detected in the central subset only, while the two others were shared. Altogether, these observations suggest that most effector memory T cells may not have derived from the central memory subset.

Adult↗
PubMed2002

Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver.

This article describes the isolation of a novel cell population (B220(lo)c-kit(+)CD19(-)) in the fetal liver that represents 70% of T-cell precursors in this organ. Interestingly, these precursors showed a bipotent T-cell and natural killer cell (NK)- restricted reconstitution potential but completely lacked B and erythromyeloid differentiation capacity both in vivo and in vitro. Moreover, not only mature T-cell receptor (TCR)alphabeta(+) peripheral T cells but also TCRgammadelta(+) and TCRalphabeta(+)CD8alphaalpha(+) intestinal epithelial cells of extrathymic origin were generated in reconstituted mice. The presence of this population in the fetal liver of athymic embryos indicates its prethymic origin. The comparison of the phenotype and differentiation potential of B220(lo)c-kit(+)CD19(-) fetal liver cells with those of thymic T/NK progenitors indicates that this is the most immature common T/NK cell progenitor so far identified. These fetal liver progenitors may represent the immediate developmental step before thymic immigration.

Animals↗
PubMed2002

Deoxyguanosine blocks allograft rejection of thymic epithelium but not lymphocyte infiltration and recognition.

Embryonic thymic lobes cultured in vitro in the presence of deoxyguanosine (dGuo) are accepted in fully mismatched recipients. The proposed explanation for this finding was the depletion of hematopoietic cells induced by the treatment associated with poor immunogenicity of thymic epithelium. We have recently demonstrated that embryonic tissues obtained at stages prior to hematopoietic colonization are nevertheless rejectable. Thymic epithelium from E10 embryos is not an exception in this respect and is acutely rejected in less than 12 days. Based on these findings we re-evaluated the protective role of dGuo against thymic allograft rejection. We observed that, in contrast to embryonic heart and intestine, allogeneic thymic epithelium naturally devoid of hematopoietic cells was accepted after treatment with dGuo. Active recognition of the allogeneic transplant was revealed by the presence of activated T cells, which infiltrated the accepted grafts, and showed reduced levels of IL-2 and IFN-gamma expression, although no essential role for IL-10 as regulatory cytokine has been found. Also, increased numbers of apoptotic cells are found in both dGuo-treated and untreated allogeneic control grafts. Moreover, the role of the indirect pathway of antigen recognition in allograft acceptance was excluded. The results show that allograft acceptance of dGuo-treated thymic lobes is induced by a direct, tissue-specific effect on the thymic stroma.

Animals↗
PubMed2002

Lymphocyte commitment during embryonic development, in the mouse.

Multipotent hematopoietic stem cells (HSC) differentiate into mature cells in the fetal liver (FL) during embryonic development, and in the bone marrow (BM) in adult animals. Multilineage differentiation is accomplished by the stepwise commitment of stem cells that sequentially loose differentiation potential. The characterization of the intermediate lymphoid precursors isolated from both hematopoietic sites suggests that, in FL, their potential of differentiation as well as their growth factor requirements are apparently less strict than in the BM. This could be the result of different commitment strategies at those sites: stochastic in the FL and instructive in the BM.

Animals↗