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At least 559 records · Page 31Linked to original sources
PubMed1993

Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination.

We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of specific CD4+ T cells by limiting dilution, and established and analyzed CD4+ T-cell clones. Bulk culture proliferation was predominantly dengue virus type 1 specific with a lesser degree of cross-reactive responses to other dengue virus serotypes, West Nile virus, and yellow fever virus. Precursor frequency determination by limiting dilution in the presence of noninfectious dengue virus antigens revealed a frequency of antigen-reactive cells of 1 in 1,686 peripheral blood mononuclear cells (PBMC) for dengue virus type 1, 1 in 9,870 PBMC for dengue virus type 3, 1 in 14,053 PBMC for dengue virus type 2, and 1 in 17,690 PBMC for dengue virus type 4. Seventeen CD4+ T-cell clones were then established by using infectious dengue virus type 1 as antigen. Two patterns of dengue virus specificity were found in these clones. Thirteen clones were dengue virus type 1 specific, and four clones recognized both dengue virus types 1 and 3. Analysis of human leukocyte antigen (HLA) restriction revealed that five clones are HLA-DRw52 restricted, one clone is HLA-DP3 restricted, and one clone is HLA-DP4 restricted. These results indicate that in this individual, the CD4+ T-lymphocyte responses to immunization with live-attenuated dengue virus type 1 vaccine are predominantly serotype specific and suggest that a multivalent vaccine may be necessary to elicit strong serotype-cross-reactive CD4+ T-lymphocyte responses in such individuals.

Adult↗
PubMed2003

An important regulatory role for CD4+CD8 alpha alpha T cells in the intestinal epithelial layer in the prevention of inflammatory bowel disease.

The normal immunoregulatory mechanisms that maintain homeostasis in the intestinal mucosa, despite continuous provocation by environmental antigens, are jeopardized in inflammatory bowel diseases. Although previous studies have suggested that intestinal intraepithelial lymphocytes prevent spontaneous intestinal inflammation, there is limited knowledge about the characteristics of regulatory cells in the intestinal intraepithelial lymphocytes population. Here we show that CD4(+)CD8 alpha alpha(+) double-positive cells present in the intestinal intraepithelial lymphocytes population can suppress T helper 1-induced intestinal inflammation in an IL-10-dependent fashion. CD4(+) T cells stimulated along the Th2 but not the Th1 lineage, when transferred to RAG-1-/- mice, acquire CD8 alpha alpha expression on reaching the intestinal epithelium, and on arrival there, augment their production of IL-10. We show that a precursor CD4(+) T cell after limited, but not repeated, stimulation by IL-4 is able to become a double-positive-regulatory cell on exposure to the intestinal microenvironment in mice. Both CD8 alpha alpha acquisition and IL-10 production depend critically on the NF-kappa B-GATA-3-axis that we have previously shown is essential for differentiation to the Th2 phenotype and for the induction of airway inflammation. Our studies identify a mechanism for the generation of regulatory T cells in the intestine that may play an important role in controlling inflammatory bowel disease.

Animals↗
PubMed2004

Ex vivo differentiated endothelial and smooth muscle cells from human cord blood progenitors home to the angiogenic tumor vasculature.

OBJECTIVES: Recent studies have provided increasing evidence that postnatal neovascularization does not rely exclusively on sprouting of preexisting vessels, but also involves bone marrow-derived circulating endothelial precursors (BM-EPCs). Animal studies revealed that neovascularization of ischemic tissue can be enhanced by BM-EPCs transplantation. But a possible limitation to the use of vascular precursors for therapeutic angiogenesis is the relatively low number of these cells. In this study, we demonstrate that ex vivo expanded differentiated endothelial cells (ECs) and smooth muscle cells (SMCs), may home to the tumor vasculature allowing targeting of transgene expression to the neoangiogenic site. METHODS: Mononuclear cells (MNCs) or CD34+ -enriched cells were purified from cord blood. We have defined culture conditions in which we observed two types of clones easily differentiated according to their morphology: cobblestone or spindle-shaped. Phenotypic characterization was assessed by immunocytochemistry, flow cytometry analysis and polymerase reaction with reverse transcription. Formation of capillary-like network in vitro was studied in three-dimensional collagen culture. And recruitment of these cells to a tumoral neoangiogenic site was assessed into tumor-bearing Severe Combined Immunodeficient (SCID) mouse model. RESULTS: The cobblestone cells uniformly positive for CD31, VE-cadherin, vWF, VEGF R1 and R2, ecNOS and incorporating acetylated LDL were ECs. Spindle-shaped cells expressed alpha-smooth muscle actin (alpha-SMA), Smooth Muscle Heavy Chain (SMHC), SM22 and calponin. They also displayed a carbachol-induced contractility in a medium containing IGF1. So we concluded that spindle-shaped cells were SMCs. ECs and SMCs interacted with each other to form a capillary like network in three-dimensional type I collagen culture. Moreover, these ex vivo differentiated cells are able to home to the tumor vasculature. CONCLUSION: We provide evidence that progenitors for ECs and SMCs circulate in human cord blood and differentiate into functional ECs and SMCs. These differentiated cells could provide a biomaterial for vascular cell therapy, because of their homing capacity to the neovascularization site.

Animals↗
PubMed1995

Import of the cytochrome oxidase subunit Va precursor into yeast mitochondria is mediated by the outer membrane receptor Mas20p.

Post-translational import of precursor proteins into yeast mitochondria is mediated by at least four protease-sensitive outer membrane proteins: Mas20p, Mas22p, Mas37p, and Mas70p. These "import receptors" recognize either the N-terminal targeting signal or some other feature of mitochondrial precursor proteins. The only exception to this general rule appeared to be the precursor to subunit Va of cytochrome c oxidase (COXVa). Although this precursor carries a typical N-terminal mitochondrial targeting sequence, its import into mitochondria has been suggested to be independent of the known import receptors. Here we show that if import into isolated yeast mitochondria is assayed under conditions in which binding of the COXVa precursor to mitochondria is rate-limiting, import is strongly inhibited by protease pretreatment of the mitochondria or by antibodies against Mas20p. Post-translational import of the COXVa precursor can thus proceed by the general, receptor-mediated pathway.

Biological Transport↗
PubMed1996

A role in migration for the alpha V beta 1 integrin expressed on oligodendrocyte precursors.

Myelination of the CNS requires the migration of oligodendrocyte precursors throughout the CNS from restricted regions within the ventricular and subventricular zones. In light of the significant effects of cell-extracellular matrix (ECM) interactions on cell migration in other developing systems, we have analyzed the role of integrins in oligodendrocyte precursor migration. We have shown previously that oligodendrocyte precursors in vitro express a limited repertoire of integrins, including alpha 6 beta 1, alpha v beta 3, and that differentiation is associated with downregulation of alpha v beta 1 and upregulation of alpha v beta 5. Using a migration assay based on the movement of cells away from an agarose drop containing a high-density cell suspension, we find that RGD peptides (that block alpha v but not alpha 6 integrins) and anti-beta 1 antibodies block migration on an astrocyte-derived ECM, whereas anti-beta 3 antibodies have little effect. These results suggest that alpha v beta 1 but not alpha 6 beta 1 plays a role in oligodendrocyte precursor migration, and this is confirmed by the use of blocking monoclonal antibodies that distinguish these two integrins. In keeping with the results of others, we find that differentiated oligodendrocytes lose migratory potential and that the timing of this loss correlates with downregulation of alpha v beta 1. Taken together with the work of others showing that ECM ligands for alpha v beta 1 are expressed within the CNS, we propose that this integrin plays a significant role in the migration of oligodendrocyte precursors in vivo and that its downregulation during differentiation could be an important factor regulating the migratory phenotype of these cells.

Animals↗
PubMed1984

Frequency of influenza-responsive cytolytic T-lymphocyte precursors in the thymus and spleen of unprimed mice.

Limiting dilution culture conditions were established which allowed the differentiation and quantitation of influenza-specific cytotoxic T-cell precursors (CTL.Ps) from naive mouse spleen and thymus. One in 49,000 nucleated spleen cells and 1 in 40,000 thymocytes responded to stimulation with influenza-infected, anti-Thy 1.2 and complement-treated spleen cells, in the presence of ConA-stimulated cell supernatant, with the production of cytotoxic effector cells. These frequencies are 4- to 15-fold higher than those for influenza-responsive B cells in the relevant lymphoid compartments, and it is argued that major quantitative discrepancies may exist in the sizes of the B- and CTL-receptor repertoires.

Animals↗
PubMed1993

Precursor trapping: a "neonatal" mechanism of myocardial protection.

During induced ischemia for cardiac surgery, 5'-nucleotidase (5NT) catalyzes nucleotide breakdown by dephosphorylating AMP and IMP to diffusible precursors--adenosine and inosine. These precursors become unavailable upon reperfusion washout limiting nucleotide resynthesis, resulting in poor postischemic function. Neonatal hearts, which are more resistant to ischemia than adults, have low 5NT activity, trapping available precursors. Adult rabbit hearts given cardioplegia with a 5NT inhibitor, pentoxifylline, demonstrated improved postischemic contractility, compliance, and myocardial oxygen consumption after 120 min of 34 degrees C ischemia. To determine if this improved function was a result of enhanced nucleotide precursor availability during or following ischemia, total nondiffusible nucleotides, ATP, ADP, AMP, and IMP, and total diffusible nucleotides, adenosine, inosine, hypoxanthine, and xanthine, were measured by HPLC at end ischemia, 1 and 15 min after reperfusion. While all preischemic values were equivalent, pentoxifylline-treated hearts had significantly greater total non-diffusible nucleotides at end ischemia, 1 and 15 min after reperfusion. Additionally, pentoxifylline-treated hearts had significantly greater total diffusible nucleosides at end ischemia and 1 min after reperfusion, but were equal to control at 15 min after reperfusion. Furthermore, coronary sinus effluent had a significantly higher release of total diffusible nucleosides in control vs pentoxifylline-treated hearts. The data indicate that precursor trapping with pentoxifylline prevented nucleotide catabolism to diffusible precursors and enhanced postischemic nucleotide availability. We postulate the increased precursor availability augmented myocardial nucleotide resynthesis and correlated with the improved functional recovery noted. This strategy may have application in adult cardiac surgery.

5'-Nucleotidase↗
PubMed1976

Transcription of specific genes in isolated nuclei from HeLa cells in vitro.

Isolated HeLa cell nuclei were employed to catalyze the synthesis of RNA in vitro. In the presence of low concentrations of alpha-amanitin (1 mug/ml), used to suppress the formation heterogeneous nRNA, these nuclei synthesize RNA very efficiently for extended periods of time (at least 60 min) at an elongation rate of about seven nucleotides per second. The product, analyzed on sucrose density gradients and polyacrylamide gels was found to exist of two predominant size classes. Synthesis of the 45-S ribosomal precursor was completely resistant even to high concentrations of alpha-amanitin (150 mug/ml) and hence was catalyzed by enzyme A (or I). A limited degree of processing of the 45-S precursor occurred in vitro. In addition, a second RNA class of low molecular weight (4-8 S) was synthesized by HeLa cell nuclei in the presence of 1 mug/ml alpha-amanitin in vitro. Analysis on 8% polyacrylamide gels resolved the RNA into four distinct components. Their synthesis was resistant to low (1 mug/ml) but clearly sensitive to high (150 mug/ml) concentrations of alpha-amanitin. Consequently the synthesis of all these small-molecular-weight RNA species is catalyzed by RNA polymerase C (or III). For the assessment of the initiation frequency of the individual classes of RNA, a new technique was developed independent of labelling the 5' end of the RNA molecule with the gamma-phosphate of the initiating nucleotide. It employs the double labelling of an RNA molecule with two different isotopes added sequentially at different stages of completion of the chain. From the incorporation ratio of the two isotopes into a particular class of RNA, conclusions can be drawn concerning their initiation frequency. The results obtained have shown a high reinitiation frequency for the small-molecular-weight RNA species at all stages of the incubation reaction. In contrast, reinitiation of the 45-S precursor RNA occurs only to a limited extent in isolated HeLa cell nuclei in vitro.

Amanitins↗
PubMed1994

Expression of meprin subunit precursors. Membrane anchoring through the beta subunit and mechanism of zymogen activation.

The biosynthesis of the membrane-bound metalloendopeptidase meprin was studied after the introduction of cDNAs encoding the rat meprin alpha and beta subunits into human 293 cells. When expressed individually the meprin alpha subunit was found to be primarily secreted into the culture medium, while the beta subunit was determined to be an integral membrane protein. Coexpression of the alpha and beta subunits results in the localization of both subunits to the plasma membrane. In this case the alpha subunit is specifically released from the cell surface by dithiothreitol, indicating the alpha subunit is associated with the membrane via disulfide bond(s) to the beta subunit. Meprin expressed in 293 cells is similar to the rat kidney enzyme in that it forms disulfide-linked dimers and has a similar pattern of glycosylation. However, the expressed protein displayed no detectable peptidase activity against four meprin substrates. Processing of the alpha subunit was followed after the introduction of sequences coding for the human c-myc peptide epitope EQKLISEEDL into its cDNA in the region of its prosequence and at the COOH terminus. Detection of the resulting proteins using a monoclonal antibody specific for the c-myc epitope indicates the alpha subunit is processed at its COOH terminus but retains the prosequence which is absent from the enzyme purified from rat kidney. Limited trypsin digestion of meprin precursors expressed in 293 cells results in both the activation of the enzyme and the removal of the prosequence. This result supports the hypothesis of Bode et al. (Bode W., Gomis-Ruth, F. X., Huber, R., Zwilling, R., and Stocker, W. (1992) Nature 358, 164-167) that meprin and other astacin family proteases require removal of NH2-terminal prosequences at the junction of the astacin protease domain for zymogen activation. Trypsin-activated meprin was assayed with the protein substrate azocasein and three synthetic peptide substrates. The membrane-bound beta subunit was found to be more active than the secreted alpha subunit against azocasein but much less active toward the synthetic peptide substrates.

Amino Acid Sequence↗
PubMed2000

Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration.

Increased accumulation of lipofuscin in cells of the retinal pigment epithelium (RPE) is seen in several forms of macular degeneration, a common cause of blindness in humans. A major fluorophore of lipofuscin is the toxic bis-retinoid, N-retinylidene-N-retinylethanolamine (A2E). Previously, we generated mice with a knockout mutation in the abcr gene. This gene encodes rim protein (RmP), an ATP-binding cassette transporter in rod outer segments. Mice lacking RmP accumulate A2E in RPE cells at a greatly increased rate over controls. Here, we identify three precursors of A2E in ocular tissues from abcr-/- mice and humans with ABCR-mediated recessive macular degenerations. Our results corroborate the scheme proposed by C. A. Parish, M. Hashimoto, K. Nakanishi, J. Dillon & J. Sparrow [Proc. Natl. Acad. Sci. USA (1998) 95, 14609-14613], for the biosynthesis of A2E: (i) condensation of all-trans-retinaldehyde (all-trans-RAL) with phosphatidylethanolamine to form a Schiff base; (ii) condensation of the amine product with a second all-trans-RAL to form a bis-retinoid; (iii) oxidation to yield a pyridinium salt; and (iv) hydrolysis of the phosphate ester to yield A2E. The latter two reactions probably occur within RPE phagolysosomes. As predicted by this model, formation of A2E was completely inhibited when abcr-/- mice were raised in total darkness. Also, once formed, A2E was not eliminated by the RPE. These data suggest that humans with retinal or macular degeneration caused by loss of RmP function may slow progression of their disease by limiting exposure to light. The precursors of A2E identified in this study may represent pharmacological targets for the treatment of ABCR-mediated macular degeneration.

ATP-Binding Cassette Transporters↗
PubMed1988

Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation.

The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.

Animals↗
PubMed1996

Plasticity of the T cell receptor repertoire in TCR beta-chain transgenic mice.

The potential alpha beta T cell receptor (TCR) repertoire in normal mice is extremely large and estimated by M. M. Davis and P. J. Bjorkman (Nature 334, 395, 1988) to include 5.2 x 10(18) different receptor molecules. This tremendous diversity provides the basis for T cell recognition of the universe of antigens including bacterial, viral, and allogeneic epitopes. Expression of a single TCR beta-chain transgene should alter the repertoire by limiting the available diversity, therefore, creating holes in the repertoire or producing TCR with decreased affinity. To determine the effect of drastically decreasing the size of the repertoire, we investigated T cell responses in TCR beta-chain transgenic mice expressing the V beta 8.2 transgene. Previous results showed that > 98% of T cells in these mice express the transgene; thus, the TCR repertoire is reduced by orders of magnitude. We tested the T cell responses of the transgenic mice and nontransgenic littermates to nine different MHC haplotypes in mixed lymphocyte reactions, five protein antigens, and eight immunogenic peptides. Surprisingly, the transgenic mice responded to all antigenic stimuli tested indicating the lack of a hole in the TCR repertoire. Interestingly, however, the response in every case was quantitatively lower than the response by the nontransgenic littermates. In contrast, transgenic and nontransgenic T cells responded equivalently to stimulation with mitogens or to stimulation with immobilized alpha-TCR mAb indicating that the transgenic T cells had a normal capacity to respond. To differentiate between decreased TCR affinity and decreased precursor frequency, we performed a limiting dilution analysis to the peptide antigens CI:NP and OVA324-339. The results showed approximately a three-to eight-fold decrease in the frequency of transgenic T cells responding to the peptide compared to nontransgenic littermates. We previously showed that the response to cI84-98 and PLP could be blocked with anti-V beta 8 mAb indicating that V beta 8.2-bearing T cells are capable of responding to peptide antigen. Analysis of TCR V alpha chain expression by PCR and flow cytometry showed similar V alpha expression in both the transgenic and the nontransgenic mice. These results demonstrate tremendous plasticity in the TCR repertoire permitting T cell responses by the transgenic mice to all antigens tested. However, the decreased magnitude of the responses may impair the capacity to defend against natural pathogens. Therefore, although the large TCR repertoire of normal mice may not be necessary to produce in vitro responses to many experimental antigens, it may confer survival benefits in natural environments.

Animals↗
PubMed1997

Antigen-specific CD8+ T cell subset distribution in lymph nodes draining the site of herpes simplex virus infection.

Inoculation with replicating virus leads to an increase in T cell numbers within lymph nodes that drain the site of infection. This increase has been associated with a nonspecific proliferation of bystander cells, with only a minority thought to be directed to the infectious agent. Such an assumption is largely based on precursor cytotoxic T lymphocyte (CTL) estimations using limiting dilution analysis. Recently, studies using more advanced molecular approaches have suggested that such functionally derived precursor frequencies considerably underestimate the proportion of T cells specific for the antigen under investigation. We have defined T cell receptor sequences characteristic of CTL populations directed to a dominant determinant of the herpes simplex virus (HSV) glycoprotein B (gB). In this investigation, we used this receptor signature as a probe to directly monitor changes occurring within lymph nodes draining the sites of active infection with HSV. We found that although lymph node CD8+ T cell numbers increase as a consequence of HSV infection, the majority of these cells are small resting cells that are not enriched for gB-specific receptors. In contrast, a significant proportion of activated T cells are highly enriched for CTL bearing gB-specific receptors. Our results are therefore consistent with a nonspecific migration of CTL precursors into the lymph nodes draining the site of infection, followed by the activation and proliferation of the antigen-specific subset that normally makes up a small proportion of the naive T cell repertoire.

Amino Acid Sequence↗
PubMed1988

Acetylcholinesterase converts Met5-enkephalin-containing peptides to Met5-enkephalin.

Acetylcholinesterase (AChE; E.C. 3.1.1.7) was incubated with a number of enkephalin-containing neuropeptides found in the bovine adrenal medulla. Met5-enkephalin and Leu5-enkephalin were the most stable of the peptides studied, while precursors of Met5-enkephalin were converted to Met5-enkephalin. AChE is therefore capable of limited peptidase activity on Met5-enkephalin precursors. The enzyme hydrolysed the Met5-enkephalin precursor BAM-12P on the C-terminal side of the pair of basic amino acid residues, and cleaved basic amino acids from the carboxy-terminal of Met5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Arg7. These results indicate that AChE, acting alone, is capable of the same pattern of enkephalin processing as that observed in the adrenal medulla.

Acetylcholinesterase↗
PubMed2006

Dynamic analysis of ABA accumulation in relation to the rate of ABA catabolism in maize tissues under water deficit.

The plant hormone abscisic acid (ABA) accumulates in plant tissues which experience water deficit (stress ABA). This study analysed its accumulation as a function of both synthesis and catabolism in maize tissues. By following the disappearance of the stress ABA when ABA synthesis was blocked by nordihydroguaiaretic acid (NDGA), the rate of the catabolism of stress ABA was determined. When compared with the catabolic rate of baseline (non-stress) ABA, stress ABA showed a catabolic rate >11 times higher. With such an elevated catabolic rate, it is proposed that the xanthophyll precursor pool may not be able to sustain the ABA accumulation, and such a proposition has been substantiated by further experiments where fluridone is used to limit the availability of upstream ABA precursors. When fluridone was used, stress ABA accumulation could only be sustained for a few hours, i.e. approximately 5 h for leaf and 1 h for root tissues. In detached roots, stress ABA accumulation could not be sustained even if fluridone was not used, suggesting that stress ABA accumulation in root systems requires the continuous import of ABA precursors from the shoots. Such an assumption was substantiated by the observation that defoliation or shading significantly reduced ABA accumulation in intact roots. The present study suggests that ABA catabolism is rapid enough to play an important role in the regulation of ABA accumulation.

Abscisic Acid↗
PubMed1985

Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning.

In this study we have determined the frequency and distribution of interleukin 2 (IL2)-producing cells and their precursors (IL2-P) in the two major subsets of human T cells. The two subsets were identified on the basis of their reactivity (or lack thereof) with anti-T4 or anti-T8 monoclonal antibodies. T4+T8- and T4-T8+ cells were first isolated from peripheral blood T cell populations by positive or negative selection using the fluorescence-activated cell sorter, and then analyzed for total IL2-P and cytolytic T lymphocyte precursor (CTL-P) frequencies using a limiting dilution microculture system which allows clonal growth of every T cell. The results indicated that 50-60% of peripheral blood T cells consisted of IL2-P. In the T4+T8- subset (which represents 60-65% of all T cells) about 75% of the cells were IL2-P, whereas about 15% of T4-T8+ cells exhibited this functional potential. In contrast, about 3% and greater than 95% of T4+T8- and T4-T8+ cells, respectively, were CTL-P. Thus, these data provide direct evidence that there is no absolute correlation between the surface phenotype and the functional potential of human peripheral blood T cells. Moreover, it is evident from this frequency analysis that a significant proportion of T4-T8+ cells have a dual functional potential. IL2-P and CTL-P frequencies were also determined in T cell populations which had been activated in allogeneic mixed lymphocyte culture. The IL2-P frequencies in total T, T4+T8- and T4-T8+ MLC populations were 30, 45 and 10%, respectively. Comparative analysis of IL2 production and CTL activity at the clonal level confirmed that up to 20% of alloreactive CTL with the T4-T8+ surface phenotype were able to produce IL2 upon specific stimulation. This dual functional capacity was also observed among T4+T8- CTL.

Antigens, Surface↗
PubMed2004

Adult stem cells.

Development of a multicellular organism is accomplished through a series of events that are preprogrammed in the genome. These events encompass cellular proliferation, lineage commitment, lineage progression, lineage expression, cellular inhibition, and regulated apoptosis. The sequential progression of cells through these events results in the formation of the differentiated cells, tissues, and organs that constitute an individual. Although most cells progress through this sequence during development, a few cells leave the developmental continuum to become reserve precursor cells. The reserve precursor cells are involved in the continual maintenance and repair of the tissues and organs throughout the life span of the individual. Until recently it was generally assumed that the precursor cells in postnatal individuals were limited to lineage-committed progenitor cells specific for various tissues. However, studies by Young, his colleagues, and others have demonstrated the presence of two categories of precursor cells that reside within the organs and tissues of postnatal animals. These two categories of precursor cells are lineage-committed (multipotent, tripotent, bipotent, and unipotent) progenitor cells and lineage-uncommitted pluripotent (epiblastic-like, ectodermal, mesodermal, and endodermal) stem cells. These reserve precursor cells provide for the continual maintenance and repair of the organism after birth.

Adult↗