bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylcholine‐binding hybridoma proteins of normal and idiotypically suppressed BALB/c mice. II. Variable region N‐terminal amino acid sequences
Authors: Kocher Hans P. , Berek Claudia , Schreier Max H. , Cosenza Humberto , Jaton Jean‐Claude 
Published: February 2007

AbstractThe murine repertoire of anti‐phosphorylcholine (PC) antibodies which do not share the TEPC 15 idiotype was analyzed by partial N‐terminal amino acid sequence determination of the variable (V) regions of five homogeneous IgM PC‐specific antibodies, which were produced by cell fusion of TEPC 15‐suppressed BALB/c spleen cells with X63‐Ag8 myeloma cells. The heavy (H) chains of three of them, HPC 16, 35 and 126, expressed an identical N‐terminal sequence (residues 140) to the TEPC 15 and all other PC‐binding myeloma proteins (PCBMP). The other two (HPC 19, 104) belonged to a new VH isotype, tentatively designated VH‐12, not seen in the library of PCBMP nor in any mouse VH region known so far. The first hypervariable region of HPC 19 and 104 was different from all those known among PCBMP, thus suggesting that the VH‐12 isotype is coded for by a separate germ‐line gene. The variable regions of the light chains (VL) displayed all V, isotypes known in PCBMP, with the exception of the V, isotype of TEPC 15. In addition, one PC‐binding hybridoma protein had the light chain isotype of the parental myeloma immunoglobulin. In the hybridoma IgM antibodies, new VH‐VL combinations not encountered among PCBMP, as well as known VH‐VL pairings of PCBMP, were expressed. The data suggest that a limited number of VH and VL regions scramble to generate the various PC‐specific antibodies. Thus, the diversity of the murine repertoire of anti‐PC antibodies may be explained at least in part by a nongenetic mechanism of VH‐VL combinatorial association.
Cross‐protection and cross‐reactive cytotoxic T cells induced by influenza virus vaccines in mice
Authors: Webster Robert G. , Askonas Brigitte A. 
Published: February 2007

AbstractSubunit and intact influenza A virus vaccines have been compared with infectious virus in a mouse model for their ability to induce memory for cross‐reactive cytotoxic T cell responses and to protect mice from challenge with different subtypes of influenza A virus. There is an overall correlation between secondary cytotoxic T cell responses and cross‐protection. The most long‐lasting and successful cross‐protection was observed after intranasal infection with influenza virus A/X31 (H3N2) that replicates efficiently in mice and induces high levels of memory for cross‐reactive cytotoxic T cell responses. Short‐lasting cross‐protection and low levels of T cell‐mediated cytotoxicity were associated with infection by A/USSR (H 1N1) virus, that replicates to lower titers in mice, or after multiple injections of inactivated whole virus vaccine. No cross‐protection to challenge with heterologous influenza virus was detectable after 1‐2 injections of HANA influenza subunit vaccine which failed to prime hosts for cytotoxic T cell responses. These findings may have important implications for vaccination strategy. If cytotoxic T cells play a role in the protection of humans from influenza, live attenuated vaccines should be considered instead of the currently recommended inactivated virus or subunit vaccines.
Indomethacin‐sensitive suppressor cells regulate the cell‐mediated cytotoxic response to SV 40‐induced tumor‐associated antigens in mice
Authors: Glaser Moshe 
Published: February 2007

AbstractSpecific secondary cytotoxic reactivity (as measured by 51Cr‐release assay) against SV 40‐induced tumor‐associated antigens was generated in vitro in spleen cells of tumor‐free (BALB/c × C57 BL/6)F1 (CBF1) mice immunized against a syngeneic SV 40‐induced tumor of BALB/c origin (mKSA), following in vitro sensitization for 5 days with the relevant antigens in mixed lymphocyte‐tumor cell cultures. In contrast, spleen cells of CBF1 mice bearing the SV 40‐induced tumor demonstrated suppressed specific secondary cytotoxic reactivity following incubation with the corresponding antigens. Spleens from tumor‐bearing mice contained 4 times the number of mononuclear cells and 3 times the percentage of macrophages, as compared to spleens of normal mice. The percentage of B cells was also elevated in spleens of tumor‐bearing mice. There was a slight reduction in the percentage of T cells. The cytotoxic reactivity of spleen cells of tumor‐bearing mice was restored following removal of macrophages by either rayon adherence columns or iron and magnet, or incubation on plastic petri dishes. No such effect was seen with spleen cells of tumor‐free or normal mice. Spleen cells of tumor‐bearing mice inhibited the in vitro generation of secondary cytotoxic reactivity of spleen cells of tumor‐free mice, sensitized in vitro with SV 40‐induced tumor cells by mixing experiments. The suppressor cells were found to be macrophages by the 3 techniques for removal of macrophages described above. The addition of indomethacin (1–10 μg/ml), a noncompetitive irreversible prostaglandin synthesis inhibitor, to cultures of responding spleen cells from tumor‐bearing mice and stimulating SV 40‐induced tumor cells resulted in marked augmentation of spleen cells responsiveness. With higher indomethacin concentrations (100 μg/ml), no enhancement was seen. The augmenting effect was noted only when indomethacin was present during the initial 24 h of the 5‐day culture. Indomethacin at 1–10 μg/ml had no effect on cytotoxic reactivity of spleen cells of tumor‐free mice, whereas at higher concentrations (100 μg/ml) it had a strong suppressive effect. Preincubation of spleen cells of tumor‐bearing mice with indomethacin for 3 days abrogated their ability to suppress the generation of secondary cytotoxic reactivity of spleen cells of tumor‐free mice. It is hypothesized that indomethacin‐sensitive suppressor macrophages regulate the immune responsiveness in tumor‐bearing mice.
Functional Thy‐1+ cells in cultures of spleen cells from nu/nu mice
Authors: Dennert Gunther , Hyman Robert 
Published: February 2007

AbstractThy‐1+ lymphocytes, detectable by quantitative serum absorption, arise in cultures of spleen cells from congenitally athymic (nu/nu) mice supplemented with supernatants from cultures of normal spleen cells stimulated with the T cell mitogen concanavalin A. Pretreatment of nu/nu spleen cells with appropriate anti‐Thy‐1 alloantibody and complement prior to culture reduces their capacity to generate Thy‐1+ cells by about 90%. This shows that the majority of cells proliferating in these cultures are descendants of Thy‐1+ cells which can be detected in the original nu/nu spleens. Experiments aimed at exploring the function of these Thy‐1+ cells after culture in conditioned medium revealed that within one or two days after culture initiation, strong cooperative activity for a humoral response to xenogeneic erythrocytes can be detected. In mixtures of bone marrow‐derived lymphocytes from various mouse strains with cultured nu/nu spleen cells, it was observed that T‐B cooperation is not H‐2‐restricted. Attempts at inducing T cell‐mediated cytotoxicity to alloantigens in such cultures of nu/nu spleen cells were unsuccessful. In contrast, nonspecific cytotoxicity which was attributed to natural killer cells was regularly observed and could be maintained in these cultures over extended periods.
A theoretical analysis of the phenotypic expression of immune response genes
Authors: Grossman Zvi , Cohen Irun R. 
Published: February 2007

AbstractThis study presents a theoretical analysis of the phenotypic expression of the products of immune response (Ir) genes linked to the major histocompatibility complex. Recent evidence indicates that animals with “low”‐responder Ir genotypes can be induced to express adequate immune responses by minor variations in the manner or site of immunization. Hence, it is unlikely that Ir genes code for defective structural products in low‐responder animals. A quantitative model is presented of the behavior of Ir genes based on two principal elements: (a) clones of lymphocytes compete for prominence through processes of growth, differentiation and feedback suppression, and (b) Ir gene products influence the affinities of lymphocyte clones for antigenic determinants, without coding for the lymphocyte receptors for antigen. The theoretical analysis of this model leads to the conclusion that small differences in affinity on the level of single cells can be amplified through differential population growth and competition between clones of cells to produce a final response that appears “all‐or‐none” on a population level. Therefore, high or low responsiveness based on Ir genes can be explained by small shifts in the strength of interaction parameters. These small shifts can result from variation in H‐2 alleles, the mode of immunization, or the array of determinants on the immunogen; factors that were observed experimentally. These shifts in interaction parameters account for the observed flexibility of phenotypic expression of Ir genes. The model explains a number of immunological observations by a few basic facts or assumptions, and avoids the problem of postulating the existence of defects to account for low responsiveness. It aims at clarifying the relationship between systemic, macroscopic observations and the underlying cellular parameters. The translation of cellular characteristics into patterns of behavior manifested by populations of cells may not necessarily result in an averaging out of the characteristics, but could also accentuate them.
Antigen‐induced feedback suppression: antigen‐specific initiator T cells fail to recruit new antigen‐reactive cells in immunized mice
Authors: Tzehoval Esther , Segal Shraga , Feldman Michael 
Published: February 2007

AbstractExperiments were carried out to investigate the control exerted by memory cells on the activation of virgin antigen‐reactive T cells. Spleen cells from normal mice, educated on human gamma‐globulin (HGG)‐fed macrophages, then injected into the footpads of syngeneic recipients, recruited antigen‐specific reactive lymphocytes in normal mice, but failed to do so in HGG‐tolerant or HGG‐immunized recipients. This inhibition of recruitment was antigen‐specific, since keyhole limpet hemocyanin (KLH) initiator lymphocytes did recruit KLH‐reactive cells in HGG‐immunized recipients. Spleen cells from immunized animals, unlike those from tolerant ones, were capable of supporting the generation in culture of HGG‐initiator lymphocytes. Hence, the suppression we observed in immunized mice cannot be simply attributed to conventional Ly 23 suppressor T cells. To analyze the mechanism of the observed suppression, we tested the capacity of initiator cells educated on macrophages fed simultaneously with KLH and HGG to recruit antigen‐reactive lymphocytes in normal as compared to immunized recipients. Such initiator lymphocytes recruited, in normal animals, both and HGG‐ and anti KLH‐reactive cells. Yet, in HGG‐immunized mice, initiator cells educated under similar conditions failed to recruit not only anti HGG‐reactive cells but also anti KLH‐reactive lymphocytes. This suggested that in HGG‐immunized recipients, stimulated by HGG initiators (or by HGG antigen), HGG memory cells may lead to the generation of a factor (or factors) which may then nonspecifically suppress the recruitment and maturation of virgin antigen‐reactive cells to unrelated antigens. This assumption is further strengthened by our findings which revealed that in the presence of HGG, spleen cells originating in HGG‐immunized mice exert a weaker mixed lymphocyte culture reaction to alloantigens. Thus, it appears that an antigen may induce, in the presence of specific activated memory cells, the generation of factors which may suppress antigen‐induced proliferation of certain T cell subsets. These results may contribute to our understanding of the possible homeostatic role played by memory T cells in feedback regulatory circuits existing among T cell subsets during immune processes. The possible role of such mechanisms in high‐ and low‐zone tolerance is discussed.
Mitogenic effects of partially purified interleukin 2 on thymocyte subpopulations and spleen T cells of the mouse
Authors: Bödeker Berthold G. D. , van Eijk Ronald V. W. , Mühlradt Peter F. 
Published: February 2007

AbstractPartially purified interleukin 2 (IL‐2) promotes proliferation of mouse spleen T, but not B cells, and of peanut‐agglutinin‐negative (PNA−), and cortisone‐resistant “mature” thymocytes, but not of PNA+ “immature” thymocytes. Within the cortisone‐resistant thymocyte population, IL‐2‐responsive cells were found in the blast cell fraction. Proliferation was measured by [3H] thymidine incorporation and subsequent increase in viable cells. The mitogenic effect of IL‐2 could not be inhibited by 50 mM methyl‐α‐D‐mannoside which excludes contaminating concanavalin A (Con A) as a cause of mitogenicity. The relative increase in viable cells in IL‐2 vs. control cultures was abrogated by 1.5 mM hydroxyurea. A possible effect of IL‐2 on cell survival is thus ruled out. IL‐2, when acting as comitogen with Con A, affected only PNA− and cortisone‐resistant thymocytes. These cells also showed high intrinsic IL‐2 release when stimulated with Con A such that a comitogenic effect of externally added IL‐2 was only seen at low cell concentrations. PNA+ thymocytes could neither be induced to release IL‐2 nor did these cells become Con A‐responsive under the influence of IL‐2, thereby excluding an IL‐2‐mediated maturation.
Individual‐specific (idiotypic) T‐B cell interactions regulating the production of anti‐2,4,6‐trinitrophenyl antibody. II. Development of idiotype‐specific helper and suppressor T cells within mice making an immune response
Authors: Gorczynski Reginald M. , Khomasurya Barbara , Kennedy Marion , Macrae Susannah , Cunningham Alastair J. 
Published: February 2007

AbstractThe previous report demonstrated that serum and cells from CBA mice immunized with trinitrophenyl (TNP), when injected into normal, syngeneic “recipient” mice, induce the formation of apparently idiotype‐specific suppressor cells and serum factors, and that such regulatory elements develop within the serum of the TNP‐immunized animals themselves. In this report, it is indicated that regulator cells develop also within the spleens of TNP‐keyhole limpet hemocyanin‐immunized animals, and may in part be responsible for our earlier observation that T cells from TNP‐immune CBA mice stimulate optimal antibody production in culture when paired with B cells from the same individual animal. While some evidence for individual‐specific T helper cells was obtained, the poorer response of mismatched T and B cells could be attributed in part to Ly‐2.2‐bearing suppressor T cells. Overall, the results support the view that idiotype‐related regulation is not confined to dominant‐idiotype models but is also involved in heterogeneous anti‐hapten antibody responses.
Flow microfluorometric analysis of alloantigen expression during T cell development
Authors: Potter Terry A. , Hogarth P. Mark , McKenzie Ian F. C. 
Published: February 2007

AbstractThe fluorescence‐activated cell sorter (FACS) was used to examine the expression of several alloantigens on T cells: Thy‐1, Lyt‐1.1, Lyt‐2.1, Ly‐5, Ly‐6 and Ly‐7. Antibodies secreted by monoclonal cell lines were used to characterize the Thy‐1.2, Lyt‐1.1 and Lyt‐2.1 antigenic determinants, whereas Ly‐5.1, Ly‐6.2 and Ly‐7.2 determinants were identified with alloantisera raised by conventional hyperimmunization. Using indirect immunofluorescence with fluorescein isothiocyanate‐conjugated reagents, the profiles obtained with the FACS demonstrated that: (a) the expression of Thy‐1 is greater on normal thymocytes than on cortisone‐resistant thymocytes (CRT), lymph node and spleen cells; (b) in contrast to Thy‐1, the expression of Ly‐1 on normal thymocytes is less than on CRT, lymph node and spleen cells; (c) about 90% of normal thymocytes but < 50% of CRT, spleen and lymph node T cells are Lyt‐2+ and (d) although weakly expressed on normal thymocytes, the amount of Ly‐6 and Ly‐7 present on peripheral T cells was considerably increased. The significance of these findings and the potential for further analysis of T cell developmental pathways is discussed.
Biochemical comparison of HLA‐DR molecules derived from autologous human T and B lymphoblasts
Authors: Altevogt Peter , Fohlman Jan , Kurnick James T. , Peterson Per , Wigzell Hans 
Published: February 2007

AbstractEarlier findings that human activated T blasts display HLA‐DR determinants have been confirmed. After phytohemagglutinin activation, Percoll gradient‐purified blast cells were cultured for two weeks in mitogen‐derived supernatants from human lymphocyte cultures. Using purified T blasts and internal labeling procedures, it was established that T blasts actively produced HLA‐DR‐like chains, as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further, HLA‐DR chains obtained from Epstein‐Barr virus‐transformed B cells and from T blasts of the same donor were compared. Two‐dimensional gel electrophoretic comparisons indicated a striking homology between 29 kD and 35 kD chains, obtained from the two different cell types. Peptide map analysis and preliminary amino acid sequence comparisons further supported this similarity. A more complete analysis would, however, be required to prove actual identity. The fact that human T blasts produce and display HLA‐DR molecules very similar, if not identical, to those present on B cells must then be incorporated into models discussing major histocompatibility complex‐restricted collaborations involving HLA‐DR molecules.
Trypanosome‐induced suppression of anti‐parasite responses during experimental African trypanosomiasis
Authors: Sacks David L. , Askonas Brigitte A. 
Published: February 2007

AbstractThe effect of Trypanosoma brucei infections on parasite‐specific antibody responses was examined by immunization of infected mice with radio‐attenuated trypanosomes of a noncross‐reacting clone. Antibody liters (total Ig) against variant surface antigen were determined by indirect immunofluorescence. The suppression resulting from acute infection was virtually complete, and is associated with the failure to control the first relapse variant of the acute clone. The suppression resulting from chronic infection was much less severe, and subsequently variant populations of the chronic clone are successfully controlled. Antibody collected 10 days after each of the first 3 peaks of parasitemia during chronic infection was titrated on the homologous parasite preparations isolated from each wave in individual mice. As the infection progressed, both IgG and IgM antibody responses to each successive wave declined. However, the decline of IgG antibody was more rapid than IgM, so that by the third parasite wave the mice were responding with predominantly, if not exclusively, low levels of IgM antibody. We conclude that the severity of trypanosome‐induced suppression of the anti‐parasite response and IgM response in particular, determines the course of infection by trypanosomes varying in virulence.
Identification and characterization of immature thymocytes responsive to T cell growth factor
Authors: Dráber Petr , Kisielow Pawel 
Published: February 2007

AbstractThe surface antigenic phenotype of peanut lectin agglutinin (PNA)‐separated, high‐density (“immature”) thymocytes which are the target for the T cell growth factor (TCGF) enabling this otherwise unresponsive cell population to mount a strong proliferative response to concanavalin A (Con A) has been studied. The results obtained indicate that (a) the major population of cells bearing the typical phenotype of immature thymocytes, i.e. low content of H‐2, high content of Thy‐1, TL, Lyt‐1 and Lyt‐2 antigens, is unable to respond to Con A in the presence of TCGF, and (b) that the responsive population constitutes a minor fraction (about 15%) of PNA+, high‐density thymocytes with surface antigenic phenotypes similar to those of mature T cells, i.e. high content of H‐2, low content of Thy‐1 and differentiated expression of Lyt antigens. Such a unique combination of properties and the presence of TL antigen on some members of the responding population suggest that it contains cells at intermediate stage(s) of differentiation between immature thymocytes and T cells.
Role of glycosylation in the H‐2‐restricted cytolysis of virus‐infected cells
Authors: Black Paul L. , Vitetta Ellen S. , Forman James , Kang Chil‐yong , May Richard D. , Uhr Jonathan W. 
Published: February 2007

AbstractThe role of the oligosaccharide portions of cell surface glycoproteins in the susceptibility of virus‐infected cells to H‐2‐restricted cytolysis was investigated by using the antibiotic tunicamycin (TM). TM inhibits the addition of sugars to the polypeptides of glycoproteins. TM treatment of P 815 cells before and during infection with vesicular stomatitis virus (VSV) inhibited glycosylation of proteins and reduced by about 50% the lysis of infected P 815 cells by VSV‐immune, H‐2‐identical killer cells. In contrast, TM treatment had a modest inhibitory effect on cytolysis of P 815 cells by alloimmune effector cells. TM treatment did not inhibit the surface expression of either H‐2 or VSV glycoprotein. Thus, glycosylation of H‐2 and/or viral glycoprotein is a prerequisite for the lysis of infected cells by H‐2‐identical, VSV‐immune cytotoxic cells.
Immunosuppressor cells from newborn mouse spleen are macrophages differentiating in vitro from monoblastic precursors
Authors: Piguet Pierre‐François , Irle Claude , Vassalli Pierre 
Published: February 2007

AbstractNewborn mouse spleen, whose cells strongly suppress the in vitro humoral response of adult spleen cells, is essentially a hematopoietic organ. It contains a large percentage of proliferating cells, among which about 50% are erythroblasts (identified by their spectrin content) and about 15% are cells of the myelocytic and monocytic lineage. Lymphoid cells are a minority, with about 20% B and only 1‐2% T lymphocytes. After 4 days, a culture of newborn spleen cells contains 5‐10 times more macrophages than that of an adult spleen. Most of these macrophage precursors from the newborn spleen are proliferating cells, partially glass‐ or plastic‐adherent, which differentiate in culture into activated macrophages producing large amounts of plas‐minogen activator. It is this macrophage excess which is responsible for the immunosuppressive effect of newborn spleen cells in culture, as indicated by (a) the effect of silica particles added to the cultures, which both relieve the suppression and prevent the accumulation of macrophages and (b) the suppression of the humoral response of adult spleen cells when they are cultured on the adherent cells from a newborn but not from an adult spleen.The suppressive effect of macrophages seems to result, at least in part, from the production of prostaglandin, since it can be relieved by indomethacin or aspirin. Suppression is not related to arginine depletion of the medium or to production of an excess of plasminogen activator. T lymphocytes from newborn spleen or lymph nodes have no suppressive capability.
The selective effect of tunicamycin on the secretion of IgM and IgG produced by the same cells
Authors: Blatt Cila , Haimovich Joseph 
Published: February 2007

AbstractCells of the hybridoma cell line X 63/38 C‐13 secreting both IgM and IgG have been used in studies on the importance of the carbohydrate moieties of the Ig molecules for their secretion. It has been found that the secretion of the IgM produced in the presence of the glycosylation inhibitor tunicamycin was strongly inhibited, while the secretion of the IgG produced by the same cells was only slightly affected.