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PubMed2000

Macrophages and their subpopulations following allogenic bone marrow transplantation for chronic myeloid leukaemia.

A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express alpha-D-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40-50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9-45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.

Adult↗
PubMed2002

Native and cloned 5-HT(3A)(S) receptors are anchored to F-actin in clonal cells and neurons.

Using selective antibodies to visualize the short isoform of the 5-HT(3A) receptor, we report here that both native and cloned 5-HT(3A)(S) receptors formed clusters associated with F-actin in all cell types studied. NG 108-15 cells expressing native 5-HT(3A)(S) receptors, COS-7 cells transiently expressing 5-HT(3A)(S) subunits, and CHO cells stably transfected with a plasmid encoding the 5-HT(3A)(S) sequence all exhibited similar surface receptor topology with 5-HT(3A)(S) receptor cluster accumulation in F-actin-rich lamellipodia and microspikes. Colocalization and coclustering of 5-HT(3A)(S) subunits and F-actin were also observed in transfected hippocampal neurons. Treatment of the neurons with latrunculin-A, a compound altering F-actin polymerization, demonstrated that 5-HT(3A)(S) receptor cluster size and topology were dependent on F-actin integrity. These results suggest that the anchoring of 5-HT(3A)(S) receptor clusters to the cytoskeletal network probably plays a key role in the physiological regulation of the receptor topology and dynamics, as is the case for other members of the 4-TMD ion channel receptor family.

Actins↗
PubMedDate not supplied

Alterations in SV40 DNA integration patterns are associated with acquisition of the invasive phenotype in hamster brain tumors.

A panel of cell lines that represents a reproducible, easily manipulated experimental system which discriminates between the minimally and diffusely invasive phenotypes of brain tumors has been developed. A population of SV40-transformed glial cells derived from newborn hamster cerebral cortex (Cx) has been sequentially passaged in newborn hamsters by intracerebral inoculation followed by in vitro culture, and after each passage progressively more invasive cell lines have been established. To study the molecular basis for the observed phenotypic characteristics associated with invasiveness, cloned cells were isolated from the first (Cx4T1-derived) and third Passage (Cx4T3-derived) cells lines. After injection into hamster brain, these cloned cells produce tumors that were either minimally invasive (Cx4T1-derived) or diffusely invasive (Cx4T3-derived) into normal brain tissue. In our initial attempt to identify and characterize the cellular and molecular factors that modulate the invasive phenotype, restriction endonuclease generated SV40 DNA-containing fragment patterns of DNA from each parental cell line and each of the clonal variants were determined by Southern transfer-hybridization. The results suggest the cell lines are composed of a limited number of tumorigenic subpopulations, each of which contain characteristic arrangements of integrated SV40 DNA with repeated in vivo/in vitro passage the avvangement of intecyvated SV40 changed. Analysis of DNA from minimally and diffusely invasive cloned cells indicated strong similarities of integrated SV40 DNA arrangement to their parental cells with the greatest similarities in cells exhibiting comparable invasive phenotypes. A striking difference was seen, however, in comparisons of SV40 DNA-containing fragment patterns of DNA extracted from clones which induced marginally versus diffusely invasive tumors. These differences suggest that the invasive cells were selected from a distinct minority subpopulation or that they may have arisen as a consequence of a more dynamic process of genetic rearrangement. This cell system appears to mimic the phenotypic and genetic heterogeneity observed in human tumors of glial origin and should prove valuable in defining the biochemical and molecular basis of tumor cell invasion.

Animals↗
PubMed2005

Phenotypic diversity, population growth, and information in fluctuating environments.

Organisms in fluctuating environments must constantly adapt their behavior to survive. In clonal populations, this may be achieved through sensing followed by response or through the generation of diversity by stochastic phenotype switching. Here we show that stochastic switching can be favored over sensing when the environment changes infrequently. The optimal switching rates then mimic the statistics of environmental changes. We derive a relation between the long-term growth rate of the organism and the information available about its fluctuating environment.

Adaptation, Biological↗
PubMed2001

Field ecology of toxic Pfiesteria complex species and a conservative analysis of their role in estuarine fish kills.

Within the past decade, toxic Pfiesteria outbreaks have been documented in poorly flushed, eutrophic areas of the largest and second largest estuaries on the U.S. mainland. Here we summarize a decadal field effort in fish kill assessment, encompassing kills related to Pfiesteria (49 major kills in North Carolina estuaries since 1991 and 4 in Maryland estuaries in 1997) and to other factors such as low oxygen stress (79 major fish kills in North Carolina estuaries). The laboratory and field data considered in developing our protocols are described, including toxic Pfiesteria behavior, environmental conditions conducive to toxic Pfiesteria activity, and impacts of toxic clonal Pfiesteria on fish health. We outline the steps of the standardized fish bioassay procedure that has been used since 1991 to diagnose whether actively toxic Pfiesteria was present during estuarine fish kills. Detailed data are given for a 1998 toxic Pfiesteria outbreak in the Neuse Estuary in North Carolina to illustrate of the full suite of diagnostic steps completed. We demonstrate that our conservative approach in implicating toxic Pfiesteria involvement in fish kills has biased in favor of causes other than Pfiesteria. Data are summarized from experiments that have shown stimulation of toxic Pfiesteria strains by nutrient (N, P) enrichment, supporting field observations of highest abundance of toxic strains in eutrophic estuaries. On the basis of a decade of research on toxic Pfiesteria, we present a conceptual model of the seasonal dynamics of toxic strains as affected by changing food resources and weather patterns. We also recommend protocols and research approaches that will strengthen the science of fish kill assessment related to Pfiesteria and/or other causative factors.

Animals↗
PubMed1996

Dynamics of the population structure of Bordetella pertussis as measured by IS1002-associated RFLP: comparison of pre- and post-vaccination strains and global distribution.

The effect of temporal and geographic factors on the population structure of Bordetella pertussis was studied using IS1002-based RFLP analysis. Among the 106 strains analysed, 36 different RFLP types were observed. For the Dutch strains, there was evidence for a shift in the population structure in time since the majority of strains were found in different families of related strains in successive periods. Most pronounced were the differences observed between 1950-1954 and later periods. This difference may have been caused by the introduction of the whole-cell vaccine in 1953, resulting in the expansion of strains which are less affected by vaccine-induced immunity. Strains with RFLP types identical to the vaccine strains were observed in the period 1950-1954, but not later, suggesting a decreased frequency of such strains due to vaccination. Analysis of strains from the 1994 Dutch pertussis epidemic revealed that 71% of the strains belonged to two RFLP types, indicating that pertussis epidemics are caused by clonal expansion. IS1002-based RFLP analysis of strains from different countries suggested a partial geographic isolation of B. pertussis populations. One RFLP type was found to have a wide distribution in time and in space.

Base Sequence↗
PubMed2004

Cryptosporidiosis: an update in molecular epidemiology.

PURPOSE OF REVIEW: Molecular tools have been developed to detect and differentiate Cryptosporidium at the species/genotype and subtype levels. These tools have been increasingly used in the characterization of the transmission of Cryptosporidium spp. This review addresses the most recent developments in molecular epidemiology of cryptosporidiosis. RECENT FINDINGS: The recent development of subtyping tools has led to better understanding of the population genetics and transmission of Cryptosporidium in humans. The population structure of C. parvum and C. hominis is apparently more complicated than previously suggested, with the likely existence of both clonal and panmictic populations. Thus, the transmission of C. parvum (genotype II) in humans is shown to be different in different areas, with zoonotic transmission important in certain places and anthroponotic transmission in others. The use of molecular tools has also led to the identification of geographic and temporal differences in the transmission of C. parvum and C. hominis, and better appreciation of the public health importance of other Cryptosporidium species/genotypes and the frequency of infections with mixed genotypes or subtypes. SUMMARY: Factors involved in the transmission of human cryptosporidiosis are difficult to examine using conventional methods. The use of molecular tools has been helpful in the assessment of the zoonotic potential of various Cryptosporidium spp. and sources of human infections, and has started to play a significant role in the characterization of transmission dynamic in endemic and epidemic areas.

Adult↗
PubMed2001

Selection of a teicoplanin-resistant Enterococcus faecium mutant during an outbreak caused by vancomycin-resistant enterococci with the vanB phenotype.

Vancomycin-resistant enterococci (VRE) have recently become an increasing problem in hospitals in Poland, being responsible for a growing number of nosocomial outbreaks. In this work, we have analyzed the second outbreak of VRE with the VanB phenotype to be identified in the country. It was caused by clonal dissemination of a single strain of vancomycin-resistant Enterococcus faecalis (VRES) and horizontal transmission of vancomycin resistance genes among several vancomycin-resistant Enterococcus faecium (VREM) strains. Two similar restriction fragment length polymorphism types of the vanB gene cluster characterized VRES and VREM isolates, and they both contained the same vanB2 variant of the vanB gene. Two vancomycin-susceptible E. faecium (VSEM) isolates, recovered from the same wards during the outbreak, proved to be related to certain VREM isolates and could represent endemic strains that had acquired vancomycin resistance. One VSEM and four VREM isolates, all identified in the same patient, belonged to a single clone, although they revealed remarkable diversity in terms of susceptibility, PFGE patterns, plasmid content, and number of vanB gene cluster copies. Most probably they reflected the dynamic evolution of an E. faecium strain in the course of infection of a single patient. One of the VREM isolates turned out to be resistant to teicoplanin, which coincided with the use of this antibiotic in the patient's therapy. Its vanB gene variant differed by a single mutation from that found in other isolates; however, it also lacked a large part of the vanB gene cluster, including the regulatory genes vanR(B) and -S(B), and the vancomycin-inducible promoter P(YB). Expression of the resistance genes vanH(B), -B, and -X(B) was constitutive in the mutant, and this phenomenon was responsible for its unusual phenotype.

Anti-Bacterial Agents↗
PubMed2000

Differential binding of clonal variants of Plasmodium falciparum to allelic forms of intracellular adhesion molecule 1 determined by flow adhesion assay.

Adhesion of Plasmodium falciparum-infected erythrocytes to the endothelial ligand intercellular adhesion molecule 1 (ICAM-1) has been implicated in the pathogenesis of cerebral malaria. Recently, a high-frequency coding polymorphism in the N-terminal domain of ICAM-1 (ICAM-1(Kilifi)) that is associated with susceptibility to cerebral disease in Kenya has been described. Preliminary static adhesion assays suggested that two different selected P. falciparum lines, ITO4-A4 (A4) and ItG-ICAM (ItG), have different properties of binding to the natural variant proteins ICAM-1 and ICAM-1(Kilifi). Using a flow adhesion assay system, we have confirmed differences between the two lines in binding of parasitized erythrocytes to the variant ICAM-1 proteins. Total adhesion of ItG-infected erythrocytes to ICAM-1 and ICAM-1(Kilifi) is greater than that of A4-infected erythrocytes, and erythrocytes infected by both parasite strains show reduced binding to ICAM-1(Kilifi). However, under these physiologically relevant flow conditions, we have shown differences between A4 and ItG strains in dynamic rolling behavior on ICAM-1(Kilifi). The percentage of erythrocytes infected with A4 that roll on both ICAM-1 and ICAM-1(Kilifi) is greater than that of those infected with ItG. Also, the rolling velocity of A4-infected erythrocytes on ICAM-1(Kilifi) is markedly increased compared to that on ICAM-1, in contrast to the rolling velocity of ItG-infected erythrocytes, which is similar on both proteins. These findings suggest that different parasite lines can vary in their avidity for the same host ligand, which may have important consequences for the pathophysiology of P. falciparum malaria.

Alleles↗
PubMed1984

Quantitative phenotypic variation in single normal and malignant cells from liver and breast occurs along a geometric series.

Single-cell variability in albumin content of normal rat hepatocytes and hepatoma cells and in a specific breast surface antigen content in normal and malignant human mammary epithelial cells was studied by a quantitative immunoperoxidase method. The range of variability was nearly 10-fold for both normal and malignant cells. This wide range of single cell heterogeneity was generated very rapidly in clonal colonies of less than 30 hepatoma cells. By a grid test for periodicity that we devised, and also by Fourier transform analysis, the distribution of albumin content in single hepatocytes and hepatoma cells, and of a breast surface antigen content in normal and malignant breast cells, was shown to be discontinuous, where the cells distributed with a periodicity that fit a geometric series, of which consecutive values differed by a factor of square root 2. The fit to this geometric series was best for normal cells. Significant quantal shifts occurred at a high rate (greater than 10(-2) per cell per generation) and to higher and lower levels with equal probability. These results demonstrate that geometric phenotypic variability is a normal phenomenon and should be taken into account when studying gene regulation and population dynamics.

Animals↗
PubMed2006

Character displacement promotes cooperation in bacterial biofilms.

Resource competition within a group of cooperators is expected to decrease selection for cooperative behavior but can also result in diversifying selection for the use of different resources, which in turn could retard the breakdown of cooperation. Diverse groups are likely to be less susceptible to invasion by noncooperating social cheats: First, competition repression resulting from character displacement may provide less of a selective advantage to cheating; second, cheats may trade off the ability to exploit cooperators that specialize in one type of resource against cooperators that specialize in another ; third, diverse communities of any kind may have higher invasion resistance because there are fewer resources available for an invader to use . Furthermore, diverse groups are likely to be more productive than clonal groups if a wider range of total resources are being used . We addressed these issues by using the cooperative trait of biofilm formation in Pseudomonas fluorescens. Character displacement through resource competition evolved within biofilms; productivity increased with increasing character displacement, and diverse biofilms were less susceptible to invasion by cheats. These results demonstrate that diversification into different ecological niches can minimize selection against cooperation in the face of local resource competition.

Biofilms↗
PubMed2002

Tissue stem cells: definition, plasticity, heterogeneity, self-organization and models--a conceptual approach.

The classical definition of adult tissue stem cells (TSC) is fundamentally based on a functional perspective. A TSC is an undifferentiated cell, capable of proliferation, self-renewal, production of a large number of differentiated functional progeny, regenerating tissue after injury and a flexibility in the use of these options. Here, we discuss the necessity for amending this definition in the light of recent insight into stem cell biology regarding stem cell heterogeneity, lineage plasticity, clonal fluctuation and cell-environment interactions. We conclude that the definition needs amendments. A decade ago the flexibility criterion has attracted little attention but recent findings have indicated its importance. Flexibility and reversibility of tissue and lineage specification (tissue plasticity) and of properties within a tissue (within-tissue plasticity) have major implications with regard to concepts of stem cell function. We advocate to give up the view of TSC as being entities with a preprogrammed development and to replace it by a concept that makes the capabilities for flexible and regulated tissue self-organization based on cell-cell and cell-environment interactions the new paradigm. This concept would permit to incorporate the context-dependent lineage plasticity, within-lineage plasticity and generation of stem cell heterogeneity as a result of a dynamically regulated process. Such concepts need a rigorous examination by formal modeling including simulation studies. We provide some general ideas on how to proceed with such theories and illustrate this with worked models for tissue stem cells of the hematopoietic system and the intestinal epithelium.

Animals↗
PubMed1992

Abnormal regional hypermethylation in cancer cells.

Let me summarize by reviewing a model which is meant to raise as many questions as it answers (Fig. 2). What I have discussed today are data suggesting that during progression of solid tumors, like colon cancer, an increased cellular DNA methylating capacity characterizes the initial stages of multi-clonal hyperplasia. Despite this increase, the altered pattern of DNA methylation which subsequently emerges is largely manifest by a widespread hypomethylation of DNA. However, on a more regional basis, areas of hypermethylation appear which can affect strategic areas such as normally unmethylated CpG islands. These shifted DNA methylation patterns have the capacity to both follow, or cause, chromatin changes that can both directly silence genes critical for normal cell maturation--and/or participate in the structural chromosome changes which constitute genetic instability during tumor progression (Fig. 2). I suggest that one must view these changes as an interchangeable cycle of events during tumor progression. The chromatin changes and abnormal methylation patterns can drive one another with increasingly deleterious effects as the malignant phenotype emerges (reviewed in Baylin, 1991). What are the molecular events that would initiate the above dynamics? A working construct model is shown in Fig. 3. As discussed for the normal adult cell, there is a delicate balance between the strategic location of DNA MTase, regulation of this enzyme, and rate of DNA synthesis at replication forks (top panel, Fig. 3). In pre-neoplastic and cancer cells, perhaps failure of cells to exit the cell cycle and halt DNA replication, facilitates some sort of pressure to increase cellular DNA methyltransferase activity (bottom panel, Fig. 3). This increase may involve loss of feedback inhibition of the enzyme during the post DNA replication phase. There are also probable structural alterations in the nucleus which may alter the geographic relationship between the DNA replication fork and DNA MTase. In consequence, many DNA areas that should be getting methylated do not, and novel areas of methylation also arise. This cycle of events leads to the imbalance of DNA methylation that I have talked about. Future investigations of these possibilities, and of their specific consequences for alterations of gene expression and chromosome structure, may reveal a key molecular step underlying virtually all stages of tumor progression.

Adult↗
PubMed1995

Clonal diversity of the Streptococcus mitis biovar 1 population in the human oral cavity and pharynx.

A total of 250 isolates of oral streptococci were recovered from swabs of oropharyngeal surfaces of 3 members of one family. All isolates were examined by biochemical and serological means, and 106 isolates were identified as Streptococcus mitis biovar 1. These were typed by restriction endonuclease analysis using the enzymes EcoRI and HaeIII and further characterized by their whole-cell polypeptide profile patterns in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, rabbit antisera raised against 8 reference strains of oral streptococci were used to characterize representative isolates both by their carbohydrate and protein antigens by Ouchterlony and Western blot analyses. Very limited biochemical diversity was observed among the 106 S. mitis biovar 1 isolates. In contrast, 24 different genotypes defined by restriction endonuclease analysis were detected, and each individual carried 6-13 types. Limited sharing of genotypes was observed between the 3 members of the same family and between the pharyngeal and buccal mucosa of single individuals. The antigenic analyses showed remarkable antigenic diversity between the 24 genotypes. The results provide a basis for studying the population dynamics of an oral commensal species and its interaction with the salivary immune system.

Adult↗
PubMed2026

Translational case series comparing next-generation sequencing profiles of primary breast cancer and brain metastases.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, and its molecular and immunohistochemical (IHC) profiles may change over time, particularly under therapeutic pressure. IHC discordance between primary tumors and BC brain metastases (BCBM) has been reported, yet its biological and clinical significance remains incompletely defined. Genomic profiling using next-generation sequencing (NGS) may provide additional insight into tumor evolution and clonal selection, although data from paired BC and BCBM are limited. METHODS: This translational case series included six patients randomly selected from an institutional cohort of BC patients who underwent neurosurgical resection of BCBM. IHC reassessment (ER, PR, and HER2) and NGS profiling using targeted panels were performed. RESULTS: Three of the six cases presented with IHC discordance, mainly loss of HR expression and gain of HER2 in BCBM. Genomic profiling identified 23 mutations in primary tumors compared with four in BCBM. BRCA1/2 variants predominated in primary tumors (21/23, 91%), most predicted to result in loss-of-function alterations. One mutation (PIK3CA/N345K) was shared between primary and metastatic tissues within the same patient. Overall survival ranged from 28 to 146 months. CONCLUSION: This paired analysis demonstrates immunophenotypic and genomic divergence between BC and BCBM, supporting the concept of dynamic tumor evolution. Receptor conversion and emergence or loss of actionable genomic alterations highlight the potential value of repeat molecular assessment in advanced stages. Although limited by a small sample size, retrospective design, and absence of matched germline testing, these findings reinforce the importance of integrating biomarker reevaluation into the management of selected patients.

Humans↗
PubMed2002

Possible mechanism for the alpha subunit of the interleukin-2 receptor (CD25) to influence interleukin-2 receptor signal transduction.

The receptors for interleukin 2 (IL-2) and interleukin 15 (IL-15) in T cells share the IL-2R beta subunit (CD122) and gamma(C) subunit but have private alpha subunits. Despite utilizing the same receptor chains known to be necessary and sufficient to transduce IL-2 signals the two cytokines manifest different cellular effects. It is commonly held that the alpha subunit of the IL-2R (CD25) is involved solely in the generation of a high affinity receptor complex. This is questioned by the development of autoimmune diseases in instances where the expression of CD25 is absent. The timely expression of CD25 in the thymus has been linked with clonal deletion. Evidence from peripheral T cells indicates that survival signals arising from the intermediate affinity IL-2R (lacking CD25) do not require the activation of Janus kinase 3 (Jak3) but do require the presence of the membrane proximal region of the gamma(C) chain. This particular signalling pathway is not observed in the high affinity receptor complex where Jak3 is activated. Recent data point to CD25 having a surface distribution consistent with it being localized within membrane microdomains. Here we suggest that in the absence of CD25 expression, IL-2R activation occurs within the soluble membrane fraction. This membrane environment and the absence of CD25 promotes Jak3 independent signal transduction and induction of antiapoptotic mechanisms. T cell antigen receptor (TCR) signalling leads to the induction of CD25 expression, which localizes to membrane microdomains. There is a dynamic pre-association of CD25 and CD122 leading to the loose association of the heterodimer with membrane microdomains. High affinity IL-2R signalling in the context of CD25 and the microdomain environment is characterized by Jak3 activation. The relative levels of high to intermediate affinity receptor signalling determines whether a cell proliferates or undergoes activation induced cell death dependent upon cell status.

Animals↗
PubMed2004

Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens.

Lineage trees of mutated rearranged Ig V region sequences in B lymphocyte clones often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation. In this study, we use a novel method for analyzing lineage tree shapes, using terms from graph theory to quantify the differences between primary and secondary diversification in rabbits and chickens. In these species, Ig gene diversification starts with rearrangement of a single (in chicken) or a few (in rabbit) V(H) genes. Somatic hypermutation and gene conversion contribute to primary diversification in appendix of young rabbits or in bursa of Fabricius of embryonic and young chickens and to secondary diversification during immune responses in germinal centers (GCs). We find that, at least in rabbits, primary diversification appears to occur at a constant rate in the appendix, and the type of Ag-specific selection seen in splenic GCs is absent. This supports the view that a primary repertoire is being generated within the expanding clonally related B cells in appendix of young rabbits and emphasizes the important role that gut-associated lymphoid tissues may play in early development of mammalian immune repertoires. Additionally, the data indicate a higher rate of hypermutation in rabbit and chicken GCs, such that the balance between hypermutation and selection tends more toward mutation and less toward selection in rabbit and chicken compared with murine GCs.

Algorithms↗
PubMed1986

Lymphocyte population kinetics in the mouse.

In a normal dynamic equilibrium, at least half of the peripheral T-cell pool is constituted by lymphocytes which have divided 24-48 h previously, and are therefore rapidly renewed. The renewal of peripheral T cells occurs partly by influx of cells from the thymus and, more importantly, by cell division at the periphery. The cyclic pattern of decay observed for T cells after HU treatment suggests the presence of progenitor-descendent relationships within the peripheral T-cell pool. Peripheral progenitors must contain both cycling and non-cycling cells to account for cell recovery after HU administration in ATx mice. T-cell production at the periphery involves both organized (spleen or lymph nodes) as well as non-organized lymphoid tissue (GALT). The latter may in fact provide the major contribution. Expansion of mature T lymphocytes contributes to clonal persistence at the periphery and to the choice of T-cell repertoires. The importance of post-thymic selection of T-cell repertoires is suggested by the considerable expansion potential revealed by peripheral T cells.

Animals↗