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Rod Ceredig

Publications and source records attributed to Rod Ceredig.

8 recordsLinked to original sources
PubMed2006

Early lymphocyte development in bone marrow and thymus.

Haematopoietic stem cells (HSCs), a very rare cell type in the bone marrow, are responsible for the life-long production of all cells of the blood including T and B cells. Until recently, it was thought that the differentiation of HSCs into the various haematopoietic cells was rather hierarchical in that differentiation along a given lineage was associated with a progressive loss of potential to give rise to other blood cell lineages. The recent development of very sensitive and quantitative in vitro assays, together with the identification of new progenitor subpopulations, has challenged this idea. Thus, lymphocyte progenitors can be shown to keep their developmental potential to give rise to myeloid, dendritic and NK cells until just prior to their final commitment stage. Here we review these new findings and concepts.

Animals↗
PubMed2005

Induction of chemokine receptor expression during early stages of T cell development.

The early events in T lineage commitment are difficult to study because of the rarity of these cells. We have therefore used cloned Pax5-/- pre-BI cell lines as a model system to study this. Stimulation in vitro of Pax5-/- pre-BI cells with stromal cells expressing the Notch ligand Delta-like 1 results in them coincidently undergoing some of the phenotypic and functional changes associated with early T cell commitment. Kinetic analysis indicated that there was a rapid induction of transcripts for the two chemokine receptors CCR4 and CXCR6. Transcripts for CCR8 increased with slower kinetics. Migration assays indicated that Delta-like 1 signalling of Pax5-/- pre-BI cells had induced responsiveness to the chemokines MDC and MIP-1beta, ligands for the receptors CCR4 and CCR8, respectively. Importantly, following Delta-like 1 signalling, similar increases in chemokine receptor transcripts were seen in a recently described bone marrow progenitor subpopulation having significant T cell progenitor activity and being phenotypically and functionally similar to Pax5-/- pre-BI cells. The relevance of these findings to studies of early T cell development will be discussed.

Cell Lineage↗
PubMed2005

Homeostatic and functional analysis of mature B cells in lambda5-deficient mice.

The peripheral B-cell pool is in dynamic equilibrium and is controlled by a variety of factors. The rate of generation of B cells can influence both the composition and size of the peripheral B-cell compartment. Mice deficient for lambda5 gene expression have a block in early B-cell development leading to a markedly reduced number of peripheral B cells. To address the question of how this early developmental block influences the composition of the B-cell pool, we have analyzed mature B-cell subpopulations in lambda5-deficient mice. In analogy with other situations of B lymphopenia, the proportion was increased but not the absolute number of marginal-zone B cells, whereas those of follicular B cells were decreased. Immunohistology revealed that B-cell follicles were smaller in overall size and contained a prominent B-cell replete marginal zone. BrdU labelling kinetics showed slower turnover of follicular as well as of marginal-zone B cells. Functionally, lambda5(-/-) mice were able to mount not only primary but also secondary thymus-dependent as well as thymus-independent responses, albeit mostly at reduced levels.

Animals↗
PubMed2005

A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential.

In this report, we identify in the bone marrow (BM) of normal mice a subpopulation of B220+ CD117+ CD19- NK1.1- cells with potent lymphoid and myeloid developmental potential. These cells represent 0.1-0.2% of nucleated BM cells. By limiting dilution analysis in the presence of the appropriate combination of stromal cells and cytokines, 1 in 5-10 sorted cells formed B cells, 1 in 10-15 formed T cells and 1 in 5-10 generated macrophages. When cultured on a mixture of OP9 stroma and OP9 stromal cells expressing the Notch ligand Delta-like-1, single cells generated both T and B cells. Following intravenous infusion, freshly sorted cells transiently reconstituted both the T and B cell progenitor compartments, generating cohorts of mature T and B lymphocytes. The relationship between B220+ CD117+ CD19- NK1.1- cells of wild-type mice and other multi-lineage BM progenitors is discussed.

Animals↗
PubMed2005

Differential expression of regulator of G-protein signalling transcripts and in vivo migration of CD4+ naïve and regulatory T cells.

The immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate to the site of infection. Thus, control of naive and regulatory CD4+ T-cell migration is crucial; however, it is poorly understood in physiological and pathological conditions. We found that CD4+ subpopulations displayed characteristic regulator of G-protein signalling (RGS) gene expression profiles. Regulatory T cells express higher levels of RGS1, RGS9 and RGS16 than naive cells. These genes are up-regulated upon cell activation and their level of expression correlates with in vivo cell migration. Using parabiosis, we showed that regulatory T lymphocytes migrate less than naive T cells and that migrant naive T cells express even lower RGS levels than their static counterparts. Our results show an inverse correlation between the capacity to migrate and the levels of RGS1, RGS9 and RGS16 for both naive and regulatory T cells. Taken together, these results suggest a role for RGS molecules in chemokine-induced lymphocyte migration and demonstrate the peculiarity of regulatory T cells in terms of phenotype and migration ability, providing new insights into their function.

Animals↗
PubMed2002

Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire.

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR alpha repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation.

Animals↗
PubMed2002

A positive look at double-negative thymocytes.

In some respects, our understanding of the cellular and molecular aspects of early T-cell differentiation is lagging behind that of B cells. Papers describing gene-knockout and reporter-transgenic mice in which thymocyte development is affected are often difficult to interpret. Progress in this field will be hampered unless a more detailed phenotypic and molecular analysis of progenitor thymocytes at the single-cell level is carried out.

Animals↗