Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood

During ageing thymic function declines and is unable to meet the demand for peripheral T helper (Th) cell replenishment. Therefore, population maintenance of naive Th cells must be at least partly peripherally based. Such peripheral postthymic expansion of recent thymic emigrants (RTEs) during ageing consequently should lead to loss or dilution of T cell receptor excision circles (TRECs) from a subset of naive T cells. We have identified two subsets of naive Th cells in human adult peripheral blood characterized by a striking unequal content of TRECs, indicating different peripheral proliferative histories. TRECs are highly enriched in peripheral naive CD45RA(+) Th cells coexpressing CD31 compared with peripheral naive CD45RA(+) Th cells lacking CD31 expression, in which TRECs can hardly be detected. Furthermore we show that CD31(-)CD45RA(+) Th cells account for increasing percentages of the naive peripheral Th cell pool during ageing but retain phenotypic and functional features of naive Th cells. As CD31 is lost upon T cell receptor (TCR) engagement in vitro, we hypothesize that TCR triggering is a prerequisite for homeostatically driven peripheral postthymic expansion of human naive RTEs. We describe here the identification of peripherally expanded naive Th cells in human adult blood characterized by the loss of CD31 expression and a highly reduced TREC content.     

TCRδ Gene Rearrangements in Acute Myeloid Leukemia with T-lymphoid Antigen Expression

In this review we present our data concerning T-cell receptor (TCR) δ gene rearrangements in acute myeloid leukemia with cuexpression of T-lymphoid features (CD2/CD4/CD7; Ly+ AML). We found a correlation between TCRδ gene rearrangements and coexpression of these T-lymphoid features. Ten of 66 Ly+ AML and only one of 44 AML cases without this coexpression exhibited TCRδ gene rearrangements (p = .028). In contrast, no correlation was observed between terminal deoxynucleotidyl transferase (TdT) expression and the occurence of TCRδ gene rearrangements in AML. Rearrangements were found in two of 25 AML with and seven of 71 AML cases without TdT expression. Interestingly, nucleotide sequencing of junctional sites revealed up to 36 N-nucleotides in cases without or with only weak TdT expression indicating downregulation of TdT expression after the TCR rearrangement took place. Complete Vδ1Jδ1 and incomplete Dδ2Jδ1 gene rearrangements were observed most frequently in Ly+ AML. These recombination patterns were similar to patterns observed in acute T-lymphoblastic leukemia with coexpression of myeloid features (My+ T-ALL) suggesting transformation of a common myeloid/T-lymphoid progenitor cell in these cases.     

The aortic bodies of spontaneously hypertensive (SHR) and normotensive rats--a study concerning location and size

The aortic bodies, including the right and left subclavian bodies and the superior aorticopulmonary bodies, were examined in inbred normotensive control rats (NCR) of the Wistar strain and in spontaneously hypertensive rats (SHR) of the OKAMOTO-AOKI strain. Paraganglia were found in all rats of either group. They were located near to the left common carotid artery and less frequently between the branching right subclavian and right common carotid artery. Superior aorticopulmonary bodies were rarely seen. No significant differences were found regarding the volume of individual aortic bodies when comparing these paraganglia in NCR and SHR. However, aortic bodies are more numerous in SHR and therefore the total volume of aortic body tissue per rat is significantly larger in this strain. There was good correlation between the total volume of aortic bodies and the total volume of carotid bodies in both strains of rats studied. These findings indicate, that the paraganglionic system as a whole is enlarged in SHR. This enlargement probably is caused genetically and not a result of increased blood pressure.     

Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history

The killer cell lectin-like receptor G1 (KLRG1) belongs to the family of inhibitory C-type lectins that are encoded in the NK gene complex. Similar to other inhibitory NK cell receptors, KLRG1 expression in adult peripheral blood lymphocytes is restricted to NK cells and to antigen-experienced T cells. Umbilical cord blood T cells are thought to represent an homogenous pool of naive T cells. Surprisingly, we identified substantial subsets of CD4 ( approximately 30%) and CD8 ( approximately 20%) alphabeta T cells in cord blood that expressed KLRG1. In contrast to T cells in adult, KLRG1(+) T cells in cord blood exhibited predominantly a naive CCR7(+)CD45RA(+) and CD11a(low) phenotype. After birth, KLRG1 expression in T cells from peripheral blood decreased rapidly to reappear in effector/memory T cells in adults. KLRG1(+) T cells in cord blood expressed a diverse T cell receptor beta (TCRbeta) repertoire and the cells proliferated normally, in contrast to KLRG1(+) T cells from adults. Finally, examination of T cell receptor excision circles (TREC) indicated that KLRG1 expression discriminated between cord blood T cells that differed in their post-thymic expansion rate. Thus, analysis of KLRG1 expression in cord blood revealed an unexpected heterogeneity of human T cells in newborns.     

Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids.

We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L-Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64-8.33.(ABSTRACT TRUNCATED AT 400 WORDS)     

Promotion of neuronal survival in vitro by thermal proteins and poly(dicarboxylic)amino acids.

Evaluating molecules for their ability to promote survival and growth of neurons, we tested thermal proteins on cultures of dissociated fetal rat forebrain neurons. (Thermal proteins are polyamino acids formed when mixtures of amino acids with minimal proportions of glutamic or aspartic acid are heated.) Thermal proteins, added to low-density cultures in serum-free medium, stimulated neurite outgrowth and induced the formation of neuronal networks which survived for 6-10 days. Neurons in control cultures failed to grow and degenerated completely within 2-4 days. Effective concentrations (EC50) of thermal proteins ranged from 3 to 100 micrograms/ml. They were equally effective when present in the medium during the culture time or after precoating of the culture dishes. A single preparation which contained only aspartic and glutamic acid was effective, and similar survival promoting actions were then found for polyglutamic acid and mixed polyamino acids containing glutamic or aspartic acid. Thermal proteins and polyglutamic acid acted in a specific manner since, under the same experimental conditions, many control peptides, proteins and growth hormones failed to promote survival of neurons. Furthermore, their effects were antagonized by heparin, but not heparan sulfate nor chondroitin sulfate. These findings suggest that sequences of successive dicarboxylic amino acid residues are able to promote survival and neurite elongation of cultured neurons and that such sequences are responsible for the survival promoting action of thermal proteins. They invite the speculation that sequences of successive dicarboxylic amino acids, while occur in many proteins and show a high degree of evolutionary conservation, may have functional role in molecular recognition processes during neuronal development.     

Supporting stabilising plate in treatment of fractures of the distal epiphysis of the radius]

The authors present a modified plate for stabilisation of compound fractures of the distal radius. The main advantages are: the simplicity of the operative technique and the possibility of early rehabilitation without any external fixation. The satisfactory results encourage further application of this technique.     

Evidence that immunoglobulin specificities of AIDS-related lymphoma are not directed to HIV-related antigens

Chronic B-cell stimulation may be a predisposing event in the early pathogenesis of the acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL). ARL-derived immunoglobulin (Ig) genes are significantly diversified from germline, suggesting that antigenic stimulation via Ig receptors may occur prior to malignant transformation. We have evaluated 6 ARL-derived antibodies for binding to human immunodeficiency virus (HIV) and cell surface epitopes. Five cases expressed IgM, and 1 case expressed IgG. Expressed V genes were significantly diversified (3%-15%) from known germline V genes. A non-Ig producing mouse myeloma cell line was transfected with expression vectors containing the lymphoma-derived V genes. By enzyme-linked immunosorbent assay and Western blot assay, the lymphoma-derived Ig's showed no reactivity against HIV recombinant proteins. Also, no specific HIV reactivity was observed by flow cytometry with lymphoma-derived Ig's against the T-cell line infected with T-tropic HIV-1 or peripheral blood mononuclear cells infected with M-tropic HIV strains, indicating lack of binding to native HIV epitopes. However, 2 of the lymphoma-derived Ig's (ARL-7 and ARL-14) bound strongly to non-HIV-infected cells of various tissue origins. Thus, these findings suggest that the transformed B cells of AIDS-associated lymphomas may not arise from the pool of anti-HIV specific B cells but, rather, may develop from B cells responding to other antigens, including self-antigens. (Blood. 2000;95:1393-1399)