bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of thymic stromal cell subpopulations grown in vitro on extracellular matrix in defined medium. II. Cytokine activities in murine thymic epithelial and mesenchymal cell culture supernatants.
Authors: Eshel I , Savion N , Shoham J 
Published: December 2022

Abstract
Two morphologically distinct primary cultures of murine thymic stroma were established and found to be of epithelial (MTEC) and mesenchymal (MTMC) origin. These cultures were generated by selective conditions of tissue disruption and were maintained on extracellular matrix in defined medium. Culture supernatants (CS) from these cultures (EC-CS and MC-CS respectively), were tested for cytokine production and for effects on thymocyte maturation. Both supernatants displayed the activities of IL-3 and of granulocyte/macrophage-CSF and not of IL-1, -2, -4, or IFN. In addition they were found to be mitogenic to murine thymocytes in a "spontaneous" [3H]TdR incorporation assay. The two supernatants differed, however, in their effect on Con A stimulation. EC-CS had a strong enhancing effect, both when used for preincubation (18 h) before Con A stimulation or when present simultaneously with it. MC-CS had a small inconsistent effect under these conditions. Also EC-CS enhanced IL-2 and IL-3 production by thymocytes. The responsive thymocyte subpopulation was the one that does not bind peanut agglutinin. CS of an established thymic epithelial cell line displayed only part of these activities at a considerably lower level. CS from primary kidney cell culture was completely devoid of activity. The results suggest that primary thymic stromal cell cultures, cultivated under the defined conditions described here, may better preserve physiologic secretory activities, and probably also other cell functions, compared with established cell lines. Furthermore, the results are compatible with the hypothesis that the soluble factors, secreted by thymic stromal cells, are active on either very early or late stages of thymic differentiation, whereas the main intrathymic stages of differentiation are conceivable dependent primarily on direct contact with stromal cells.
The T cell repertoire to a multideterminant antigen. Clonal heterogeneity of the T cell response, variation between syngeneic individuals, and in vitro selection of T cell specificities.
Authors: Gammon G , Klotz J , Ando D , Sercarz E E 
Published: December 2022

Abstract
The specificity of lysozyme-induced T cell proliferative responses by individual B10.A mice was compared by using a panel of three peptides. A surprising degree of variation in the focus of the responses was observed among individual animals, both in the newly isolated lymph node cell populations and in long term T cell lines. The responses to each determinant after hen egg-white lysozyme immunization were not equal and in examining the mice as a group some determinants tended to be dominant. However, despite each animal favoring a restricted number of determinants, the responding T cell populations were still highly heterogeneous. The data suggest that many determinants are involved in the response to the whole Ag. The role of one or more dominant determinants can be overestimated because the degree of heterogeneity in long term T cell lines appears to be less than in freshly obtained lymph node cells, indicating that a process of in vitro selection occurs. We observed that the T cells responsive to one peptide, 46-61, appeared to have a selective advantage in vitro culture.
IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation.
Authors: Rothenberg E V , Diamond R A , Pepper K A , Yang J A 
Published: December 2022

Abstract
The ability to express the growth hormone IL-2 upon stimulation gives T lymphocytes one of their major effector functions in the immune system. IL-2 is apparently synthesized only by T cells, and only by a subset of T cells which constitutes a "helper" class. It remains unknown how and when the IL-2-producing lineage becomes distinct from other functional effector lineages. We have therefore examined immature T cell precursors to determine when IL-2 inducibility is acquired in relation to other maturation events, such as expression of an Ag-binding TCR, which is suspected to play an influential role in the determination of subclass commitment. In mature T cells, IL-2 is inducible via agonists of the phosphoinositide pathway, a network of signaling mediators shared by a wide variety of metazoan cell types. The universality of this activation pathway makes it seem less likely, a priori, to be a target of developmental change than the intrinsic susceptibility to induction of the IL-2 locus. However, our results presented here refute this expectation. In this report, we show that both TCR+ cells and pre-T cells too immature to express TCR can be induced to express IL-2 at high levels. The induction requirements for IL-2 expression, however, are different in TCR- and TCR+ cells. Even by using Ca2+ ionophore and phorbol ester to bypass the requirement for the TCR in cell activation, the TCR- cells also require the presence of the polypeptide hormone IL-1. By contrast, TCR+ mature cells not only can express IL-2 without IL-1, but also show no response to IL-1 when Ca2+ ionophore and phorbol ester are present. IL-1-dependent IL-2 producers appear in the thymus of repopulating radiation chimeras before "mature" (TCR+) T cells, whereas IL-1-independent IL-2 production is found only afterward. Thus, IL-2 inducibility per se apparently precedes TCR expression and all TCR-associated fate determination events. However, developmental alteration of signal transduction pathways may play a vital regulatory role in the later allocation of particular functional responses to appropriate lineages of T cells.
Zidovudine (azido dideoxythymidine) inhibits characteristic early alterations of lymphoid cell populations in retrovirus-induced murine AIDS.
Authors: Portnoi D , Stall A M , Schwartz D , Merigan T C , Herzenberg L A , Basham T 
Published: December 2022

Abstract
Using flow cytometry technology and multiparameter analyses, we report early and characteristic alterations in lymphoid cell profile in spleen and lymph nodes due to LP-BM5 retrovirus disease (murine AIDS (MAIDS)) and the effect of azido dideoxythymidine, a nucleoside inhibitor, on these changes. MAIDS has been characterized by rapid and profound lymphoproliferation accompanied by hypergammaglobulinemia and immunosuppression. As early as 2 wk postinfection, there is a selective depletion of CD8+ cells whereas the total number of CD4+ cells increases throughout the first 8 wk of infection although the frequency is relatively stable. These population changes were partially delayed by oral AZT therapy for 6 wk postinfection. Ly-6C (AL-21) is expressed on roughly 50% of CD4+ and CD8+ cells in C57BL/6 mice. In MAIDS, the residual population of CD8+ cells is primarily Ly-6C+. The CD4+ cells have a transient increase in ratio of Ly-6C+/Ly-6C- cells at 2 wk postinfection but by 6 wk are primarily Ly-6C-. There was an increase in both the total number and percentage of Mac 1+ cells and a selective depletion of certain splenic B cell subpopulations. Azido dideoxythymidine delays these early population changes.
Both ongoing suppression and clonal elimination contribute to graft-host tolerance after transplantation of HLA mismatched T cell-depleted marrow for severe combined immunodeficiency.
Authors: Rosenkrantz K , Keever C , Bhimani K , Horvath A , Brochstein J , O'Reilly R , Dupont B , Flomenberg N 
Published: December 2022

Abstract
Lymphocytes from children with severe combined immunodeficiency who had been immunologically reconstituted with haploidentical T cell-depleted bone marrow were analyzed with regard to their immunologic recognition of donor, host, or third party alloantigens. When compared with freshly isolated donor lymphocytes, the engrafted donor cells exhibited markedly reduced to absent responses toward host Ag in primary or secondary MLC and cell-mediated lympholysis assays. However, under limiting dilution conditions, cytotoxic responses to host Ag could be demonstrated, indicating that small numbers of host reactive cells were present, although down-regulated at high responder cell doses. These results are consistent with prior observations in limiting dilution cultures that indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. The number of host reactive cells present in these patients is significantly less than that present in cells isolated directly from the marrow donors, and is also less than the number of autocytotoxic cells normally seen in peripheral blood. Together, these observations indicate that two mechanisms contribute to donor host tolerance in these patients. The majority of host reactive cells appear to have undergone clonal deletion or inactivation, whereas the small residual host-reactive population appears to be under ongoing immunoregulatory control.
Effects of recombinant murine tumor necrosis factor-alpha on immune function.
Authors: Gordon C , Wofsy D 
Published: December 2022

Abstract
TNF-alpha is a macrophage-derived cytokine with diverse biologic activities, including potent immunomodulatory effects. In vitro studies have implied that TNF-alpha has predominantly proinflammatory and immunostimulatory effects, but paradoxically in vivo studies have demonstrated that administration of TNF-alpha suppresses murine lupus. To assess the effects of TNF-alpha on immune function in normal mice, we treated C57BL/6 mice with recombinant murine TNF-alpha (10 micrograms i.p.) or PBS on alternate days for up to 8 wk. Administration of TNF-alpha decreased the percentage of splenic T and B cells and increased the percentage of splenic macrophages without significantly altering the total number of mononuclear cells. Administration of TNF-alpha also caused progressive inhibition of splenic lymphocyte function, out of proportion to the quantitative reduction in B and T cells. After 8 wk of therapy, the proliferative responses of splenic lymphocytes to Con A, PHA, and LPS were reduced by 100, 90, and 60%, respectively, in treated mice compared with control mice. The reduction in T cell proliferation was due primarily to alteration of accessory cell function rather than direct inhibition of T cell function. Treatment with TNF-alpha markedly inhibited T cell cytotoxicity induced by immunization with allogenic target cells, and it virtually ablated NK cell activity. Inhibition of these in vitro tests of lymphocyte function correlated with inhibition of delayed type hypersensitivity in vivo. In contrast, treatment with TNF-alpha did not impair humoral immunity. These findings imply that TNF-alpha may affect cell-mediated immunity more profoundly than humoral immunity. This observation may be relevant to the mechanism whereby TNF-alpha suppresses murine lupus.
Purification of 1F5 antigen that prevents complement attack on homologous cell membranes.
Authors: Harada R , Okada N , Fujita T , Okada H 
Published: December 2022

Abstract
A mAb, 1F5, has the ability to cause hemolysis by human serum of human E treated with neuraminidase via the alternative C pathway. By Western blotting, this mAb reacts with a glycoprotein having a molecular mass of 20 kDa (1F5Ag). 1F5Ag was isolated from human E by affinity chromatography with mAb-coupled Sepharose. Purified 1F5Ag was then adsorbed to guinea pig E rendering them resistant to human C attack by both the classical and the alternative pathways. Furthermore, experiments with isolated C components revealed that 1F5Ag interferes with both homologous human C8 and C9 in the terminal stage of the C reaction, whereas it has little effect on hemolysis by rabbit C8 and C9. Therefore, 1F5Ag can be called HRF20, which stands for homologous restriction factor of 20 kDa.
Comparative structure of two duplicated T1a class I genes (T10c and 37) of the murine H-2d MHC. Implications on the evolution of the T1a region.
Authors: Nakayama K , Tokito S , Jaulin C , Delarbre C , Kourilsky P , Nakauchi H , Gachelin G 
Published: December 2022

Abstract
The class I Ag encoded in the Qa/T1a regions of the murine MHC are much less polymorphic, and usually have a more restricted tissue distribution than the classical histocompatibility class I Ag, encoded by genes located in the H-2K, D, and L loci. The isolation of a quasi-ubiquitously expressed, poorly polymorphic class I gene of the T1a region of the H-2d mouse MHC, namely gene 37 (or T18d), has been recently reported. We describe the nucleotide sequence of a closely related gene, T10c gene, the counterpart of the gene 37 in the large duplicated parts of T1a region of the BALB/c (H-2d) MHC. The T10c gene structure and sequence are very similar to those of gene 37, but T10c gene is most likely a pseudogene. In A/J mouse strain, there appears to be a single gene related to 37, which is also found expressed in a variety of tissues. We show that this gene is likely to be a chimeric one derived from T10c for its 3' part, and from a gene closely related to gene 37 for its 5' part, which potentially encodes for an unusual class I molecule composed of the first two domains. Finally, Southern blot analysis of a number of wild mice and related animals suggests that a gene closely related to the present T10c gene may be the ancestor of this subfamily of class I genes characterized by the presence of an unusual second domain.
Regulation of T cell proliferation by IL-7.
Authors: Grabstein K H , Namen A E , Shanebeck K , Voice R F , Reed S G , Widmer M B 
Published: December 2022

Abstract
The regulation of murine T cell proliferation by IL-7 was investigated. Highly purified resting splenic T cells were induced to proliferate in a short term assay by IL-7 in the presence of the comitogen, Con A. The proliferation of these resting T cells showed both IL-2-dependent and -independent components as determined by the susceptibility of the response to the blocking effects of anti-IL-2 mAb. Furthermore, IL-7 was found to augment the Con A-induced production of IL-2 and expression of IL-2R by resting splenic T cells. In contrast, Con A blasts and long term, Ag-dependent cloned T cells proliferated in response to IL-7 independently of any involvement of IL-2. Finally, differences were observed between IL-7 and IL-6 with regard to the regulation of T cell growth and activation. As with IL-7, IL-6 stimulated resting splenic T cells to proliferate in the presence of comitogen. However, in contrast to IL-7, IL-6 failed to stimulate the proliferation of Con A blasts or T cell clones and did not augment the Con A-induced expression of IL-2R on resting T cells.
The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing.
Authors: Benjamin W H , Hall P , Roberts S J , Briles D E 
Published: December 2022

Abstract
The Ity locus affects the net increase in numbers of Salmonella typhimurium in the liver and spleen of infected mice. There has been controversy, however, about whether the effects of this locus are due to differential killing of S. typhimurium or differential growth rates of S. typhimurium in mice. Our studies using S. typhimurium aroA mutants, which do not grow in vivo, demonstrate that growth of the infecting salmonella is necessary for the observation of the Ity phenotype. To examine the effects of the Ity locus on the growth and killing of fully virulent salmonella, we infected Ity-congenic mice i.v. with stationary phase S. typhimurium containing a single copy of the plasmid pHSG422. This plasmid exhibits defective replication at body temperature and is diluted out during salmonella growth in vivo. Thus, the frequency of plasmid-containing salmonella recovered from mice provides a measure of salmonella cell divisions in vivo. Inasmuch as the numbers of plasmid-containing salmonella are only slightly affected by bacterial division, any decline in the numbers of plasmid-containing salmonella is an unbiased measure of killing. By infecting mice with these plasmid-containing salmonella we observed that: 1) during the first four h post infection (during blood clearance of injected salmonella) there is about 3-fold more killing of salmonella in Ityr mice than in Itys mice; 2) from 4 to 44 h postinfection (after blood clearance is completed) there is little if any additional killing in either Itys or Ityr mice; and 3) during the first 48 h postinfection there is about 18-fold more growth of salmonella in Itys mice than in Ityr mice. Thus, the major effect of the Ity locus on resistance to salmonella, is the regulation of growth within a "safe" (relatively nonbactericidal) site in the liver and spleen.
Nucleotide sequence and T cell epitopes of a membrane protein of Francisella tularensis.
Authors: Sjöstedt A , Sandström G , Tärnvik A , Jaurin B 
Published: December 2022

Abstract
A 17-kDa major membrane protein of the facultative intracellular bacterium Francisella tularensis is recognized by T cells from individuals previously undergoing tularemia or tularemia vaccination. Here the nucleotide sequence of the encoding gene is presented. The A + T rich sequence deduced a protein of 149 amino acids with a predicted m.w. of 15,772. Evidence is presented suggesting that the 17-kDa protein is a lipoprotein. Also, homology was found to a peptidoglycan-associated lipoprotein of Escherichia coli. Thirteen overlapping synthetic peptides encompassing the entire deduced protein were tested on lymphocytes from F. tularensis-primed individuals. Three peptides induced a T cell response, as disclosed by lymphocyte proliferation and production of IL-2 and IFN-gamma. Out of five responding individuals, only one recognized more than one of the peptides. A murine mAb recognized an epitope separate from the T cell-reactive peptides. The identified T cell epitopes are presumably relevant to the host defense against F. tularensis, especially because IFN-gamma is known to enhance the antimicrobial activity of the host against intracellular bacteria.
The BM12 mutation and autoantibodies to dsDNA in NZB.H-2bm12 mice.
Authors: Chiang B L , Bearer E , Ansari A , Dorshkind K , Gershwin M E 
Published: December 2022

Abstract
Molecular and genetic tools have been used to shed light on the genes that contribute to susceptibility to murine lupus and the mechanisms that lead to immunopathology. The MHC genes and their products have been consistently shown to contribute toward the development of disease. To understand the contribution of MHC-class II genes, our laboratory had derived two inbred strains of mice, NZB.H-2bm12 and NZB.H-2b. These new colonies of mice were studied and compared in the 10th generation backcross; inbreeding was serially followed by H-2 typing, responses to beef/porcine insulin, and the presence of the B6 Ig allotype, IgG2ab. Of great interest is the finding that NZB.H-2bm12, in contrast to NZB.H-2b or NZB (H-2d), mice develop high titer autoantibodies to dsDNA. This result is unique because NZB (H-2d) mice, unliked NZB x NZW (NZB/W F1) or NZB x SWR (SNF1) hybrids do not develop autoantibodies to dsDNA, even after immunization. NZB mice, in contrast, are characterized only by autoantibodies to ssDNA. Our observation is also striking because the gene conversion that resulted in the I-A beta bm12 mutation occurred at amino acid residues 68, 71, and 72 of I-E beta b. Recently the contribution of NZW to accelerated autoimmunity in the NZB x NZW F1 hybrid has also been linked to H-2 and a single amino acid change at amino acid 72 of I-E beta. Thus, amino acid residue 72 may be a hot spot for disorders of immune regulation when superimposed on the appropriate genetic background. NZB mice expressing the I-Abm12 mutation will allow specific dissection of the requirements for autoantibody production to dsDNA uncomplicated by heterozygosity.
IL-5 induces a Pgp-1 (CD44) bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds to hyaluronate.
Authors: Murakami S , Miyake K , June C H , Kincade P W , Hodes R J 
Published: December 2022

Abstract
Pgp-1 expression was examined in unstimulated B cell populations and in B cells activated with several polyclonal stimuli. Flow cytometry analysis demonstrated that Pgp-1 expression increased when B cells were activated with supernatant of cloned Th2 cells, with LPS, or with IL-5, stimuli that induced polyclonal proliferation and differentiation. IL-5-primed B cells were phenotypically unique and could be divided into two distinct subpopulations based on the brightness of Pgp-1 expression. Furthermore, sterile sorting experiments showed that proliferating and differentiating B cells were highly enriched in a Pgp-1-bright, Ia-dull, B220-dull subpopulation. The possibility that Pgp-1 expressed on activated B cells functions as an adhesion molecule was evaluated by assessing adhesion of activated B cells to defined substrates. It was found that IL-5-activated B cells bound strongly to hyaluronate-coated surface, and this binding was specifically inhibited by anti-Pgp-1 Ab. These findings suggest that Pgp-1 expression is a useful marker which, under defined conditions, identifies the proliferating and differentiating subset of activated B cells. Moreover, the Pgp-1 bright subset of IL-5-primed B cells binds to hyaluronate in a Pgp-1-dependent manner that suggests a potential role of Pgp-1 in the in vivo adherence and trafficking of activated B cells.
Rapid loss of IgM expression by normal murine B cells undergoing IgG1 and IgE class switching after in vivo immunization.
Authors: Snapper C M , Finkelman F D 
Published: December 2022

Abstract
Injection of mice with polyclonal goat anti-mouse IgD antibody (G alpha M delta) stimulates a potent T cell-dependent immune response characterized by large increases in serum IgG1 and IgE concentrations and by the generation of substantial numbers of membrane (m)IgG1+ B cells. The onset of this response occurs 6 days after G alpha M delta injection and peaks by day 7 to 8. Utilizing two color fluorescence analysis and cell sorting we demonstrate that most mIgG1-expressing B cells lack mIgM during the period of onset of Ig isotype switching (day 6). Both IgG1 and IgE are produced predominantly by mIgM- cells. On day 6, IgG1 and IgE are secreted predominantly by cells expressing mIgG1 and mIgE, respectively. By day 8, a majority of the IgG1 secretion occurs among the mIgG1- cells but virtually all IgE secretion continues to come from the mIgE+ population. B cells that strongly express mIgG1 secrete little IgM or IgE. Freshly harvested B cells expressing mIgG1, 6 days after G alpha M delta injection, have undergone substantial deletion of CH mu-specific DNA in contrast to their mIgG1- counterparts. Hence, the great majority of B cells that switch to the IgG1 or IgE isotypes in vivo rapidly lose their expression of IgM.