bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 2 and interferon‐γ are not sufficient to induce natural killer‐like activity in human T cell clones
Authors: López‐Botet Miguel , Toribio Maria Luisa , Moretta Lorenzo , De Landázuri Manuel O. 
Published: February 2007

AbstractThe role of interleukin 2 (IL2) and interferon (IFN)‐γ in the maintenance of natural killer (NK)‐like activity mediated by human cytolytic T cell clones was investigated. When cultured in standard supernatant (SN) obtained by phytohemagglutinin stimulation of human mononuclear cells (containing both IL2 and IFN activities), several mixed lymphocyte culture‐derived clones displayed cytolytic activity directed against the K562 cell line; in addition, some of these clones also lysed specific target cells bearing the sensitizing alloantigens. When cultured in IL 2‐containing SN obtained from the Jurkat cell line, the NK‐like activity was selectively abrogated within 4–5 days. However, by culturing cells again in standard SN the cytolytic activity was completely restored. The possibility that inhibitory molecules in Jurkat SN could be responsible for the loss of NK‐like activity was ruled out by experiments showing that cytotoxicity could be induced by mixtures of Jurkat and standard SN. In addition, a source of affinity chromatography‐purified IL2 also failed to maintain NK‐like activity. Moreover, addition of recombinant IFN‐γ in combination with purified IL2 did not prevent the loss of NK‐like activity. The present results indicate that neither IL2 nor IFN‐γ are sufficient to maintain NK‐like activity and suggest that other molecule(s) are required.
Selective and polyclonal induction of high levels of λ light chain‐bearing immunoglobulins in BALB/c and SJL mice
Authors: Primi Daniele , Sanchez Pierre , Cazenave Pierre‐André 
Published: February 2007

AbstractPolyclonal B cell activation is V gene independent and consequently results in the unselected expression of both Vλ and Vϰ genes. In an attempt to selectively and polyclonally trigger λ light chain‐bearing B cells, we immunized mice with low doses of lipopolysaccharide (LPS) coupled to antibodies specific for the constant region of λ1 chains. Analyses of the sera of treated mice revealed that LPS anti‐λ1 selectively triggers λ‐ but not ϰ‐bearing B cells to high rate Ig secretion. Surprisingly, immunized SJL mice (r phenotype) mounted a λ+ response comparable to that detected in mice with the phenotype. Because we could definitively establish that the majority of the induced antibodies belong to the λ1 subtype, our results have strong implications both for the study of the repertoire of λ1‐bearing B cells and for our understanding of the functional mechanism(s) by which the rλ1 locus acts.
Activation of macrophage tumor cytotoxicity by the synergism of two T cell‐derived lymphokines: Immune interferon (IFN‐γ) and macrophage cytotoxicity‐ inducing factor 2 (MCIF2)
Authors: Hamann Ute , Krammer Peter H. 
Published: February 2007

AbstractThis report describes the role of T cell‐derived lymphokines in induction of macrophage (Ma) tumor cytotoxicity. M tumor cytotoxicity was tested with the murine Ma‐like tumor PU5‐1.8. This MΦ‐like tumor reacts to stimulation with T cell‐derived lymphokines and shows tumor cytotoxicity comparable to resident peritoneal MΦ. The experiments demonstrate that immune interferon (IFN‐γ) secreted by T cell clones in limiting dilution microcultures was insufficient to induce MΦ tumor cytotox icity. Induction of MΦ tumor cytotoxicity by T cell‐derived supernatants with quantities of IFN‐γ undetectable in the IFN assay, however, was completely inhibited by an antiserum raised against recombinant IFN‐γ. Taken together, these results could be thus explained: (a) a T cell‐derived lymphokine distinct from but serologically cross‐reactive with IFN‐γ induces MΦ tumor cytotoxicity, and (b) IFN‐γ activity in supernatants positive for induction of MΦ tumor cytotoxicity escapes detection in the IFN assay but can still be inhibited by the anti‐IFN‐γ antiserum in the MΦ tumor cytotoxicity assay. The latter explanation requires positive evidence for another T cell‐derived lymphokine inducing MΦ tumor cytotoxicity together with IFN‐γ. This lymphokine was found in the supernatant of T cells in limiting dilution cultures and a long‐term T cell clone and was called Mγ cytotoxicity‐inducing factor 2 (MCIF2). MCIF2 synergizes with IFNγ induction of MΦ tumor cytotoxicity; IFN‐γ and MCIF2 alone were ineffective.
Cytotoxic T cell clone‐specific monoclonal antibodies used to select clonotypic antigen‐specific cytotoxic T cells
Authors: Acha‐Orbea Hans , Zinkernagel Rolf M. , Hengartner Hans 
Published: February 2007

AbstractTwo rat monoclonal antibodies (mAb) have been produced which recognize a clonespecific determinant on the alloreactive cytotoxic T lymphocyte (CTL) clone 3F9. CTL clone 3 F9 of BALB/c origin is specific for H‐2Db and can be grown by weekly restimulation with irradiated stimulator spleen cells expressing H‐2Db in the presence of interleukin 2. Two mAb against T cell clone 3F9, 44‐22‐l(IgG2a) and 46‐6 B5(IgM), have been proven to be clone specific: they inhibit cytotoxic activity of 3F9 only and bind specifically to 3 F9 when compared in a panel of different CTL clones, or cells from different mixed lymphocyte cultures (MLC), BALB/c thymus and spleen cells. The mAb 44‐22‐1 has been used to sort cells from a primary MLC BALB/c anti‐ H‐2Db by fluorescence‐activated cell sorter (FACS) to select CTL expressing 3 F9 clonotype‐specific determinants. The lymphocytes reactive with 44‐22‐1 represent a minor subpopulation of the CTL of the primary MLC. The specific alloreactive cytotoxicity of unsorted lymphocytes of the bulk primary MLC could not be inhibited by the mAb 44‐22‐1 and 46‐6 B5 whereas the sorted 3 F9 clonotype‐positive cultures could be inhibited very effectively. All the CTL clones derived from the FACS‐sorted clonotype‐positive culture show all the same properties and are identical with clone 3F9 with respect to antigen‐specific cytotoxicity, inhibition of cytotoxicity by the mAb and surface markers.
T cell‐replacing factor in specific antibody responses to influenza virus by human blood B cells
Authors: Cailard Robin E. , Booth Roger J. , Brown Marion H. , McCaughan Geoffrey W. 
Published: February 2007

AbstractIn man, B cell maturation factors obtained from T cells or T cell lines have been shown to induce antibody formation in mitogen or anti‐immunoglobulin activated B cells, and in some continuous B cell lines, but the relationships between these factors and B cell differentiation factors in antigen‐specific antibody responses is unclear. We have now shown that supernatants from phytohemagglutinin‐activated tonsil cells, or from the Gibbon Ape T cell line ML A‐144, can substitute for T cells in the specific antibody response by human blood B cells to influenza virus. Thus, T cell‐depleted non‐rosette‐forming (E−) cells prepared from peripheral blood mononuclear cells made antibody when cultured with antigen and factor together, whereas control cultures of E− cells with either antigen or factor alone did not. Moreover, E− cells cultured with factor and influenza virus strain A/X31 made antibody to A/X31, but not the non‐cross‐reacting strain, B/HK (and vice versa)showing that the response was antigen specific. The activity in these supernatants, therefore, fulfilled the functional definition of T cell‐replacing factor (TRF). The possibility that interleukin 2 (IL2) present in the TRF‐containing supernatants was expanding residual T cells in the E− preparations to provide normal T cell help was excluded in three different ways. First, E− cells depleted of T (Leu4+) cells to undetectable levels made normal amounts of antibody when cultured with antigen and TRF. Secondly, a limiting dilution technique was employed to show that help in cultures of E− cells and TRF was not mediated by antigen‐specific T helper cells. Thirdly, TRF‐containing supernatants depleted of IL2 retained activity, whereas purified IL2 was inactive. Preliminary purification of TRF by gel filtration on Ultrogel AcA54 columns showed that all the activity eluted in a single peak between 35000 and 43000 molecular weight. This distinguishes human TRF from IL2 and from other B cell maturation factors with a molecular weight range of 15000–20000 which act on continuous B cell lines.In addition to TRF, supernatants from phytohemagglutinin‐activated tonsils also contained a factor which could induce polyspecific IgM production, but only in cultures containing significant numbers of T cells. This additional activity may have been due to IL2, and provides an explanation for the apparent T cell‐dependent effects sometimes observed in experiments designed to test B cell differentiation factors on T cell‐ depleted normal B cells.
Rat natural killer cell and cytotoxic T cell lysis of H‐2‐negative murine embryonal carcinoma cells
Authors: Bell Susan M. , Stern Peter L. 
Published: February 2007

AbstractH‐2‐lacking murine embryonal carcinoma (EC) cells have been proposed as universal targets for natural killer (NK) effectors from different species because their killing appeared to be uncomplicated by potential T cell effector mechanisms (Stern, P. L. et al., Int. J. Cancer1981. 27: 679). While some previous studies had shown that murine cytotoxic T cells were unable to lyse EC cells, rat T killers are shown here to be active against these targets and to be distinguishable from NK cells.Percoll density fractionation of rat peripheral blood lymphocytes enriches in parallel for NK‐mediated lysis of both EC or YAC target cells. These NK cells, unlike T cells, do not mediate lectin‐dependent and cell‐mediated cytotoxicity (LDCC) of NK‐insen‐ sitive target cells. This procedure is thought to reveal the total cytolytic potential of stimulated T cell populations, regardless of specificity. In contrast to previous results with mice, we found that allogeneically primed rat cytotoxic T cells can kill murine EC cells in LDCC and, further, that rat cytotoxic T cells, generated by stimulation with mouse spleen cells in vitro, can lyse murine EC cells directly.This demonstration of T cell lysis of EC cells suggests that either there is a novel mechanism of lysis operating without requirement for major histocompatibility com‐ plex (MHC) structures, or EC cells express some hitherto unidentified MHC‐like structures on their cell surface.
Clones of B lymphocytes in individual follicles of the bursa of Fabricius
Authors: Pink J. Richard , Vainio Olli , Rünbeek Anne‐Marie 
Published: February 2007

AbstractTo discover whether individual bursal follicles can contain clones of B lymphocytes, we estimated the numbers of lymphoid cell precursors populating single follicles in two types of chicken chimera. The first type was produced by establishing parabiotic connections between blood vessels of embryo chorioallantoic membranes. Under these conditions, and most likely during normal development, most follicles are populated by more than one, but less than ten, precursor cells. However, in a second type of chimera, a cyclophosphamide‐treated chick reconstituted with normal bursal cells, most follicles in the reconstituted bursa are clonal (their lymphocytes are derived from a single precursor cell). Individual follicles can readily be isolated from bursae of reconstituted birds and should be useful in studies of B cell development.
Capacity of small B cell‐enriched populations to stimulate mixed lymphocyte reactions: marked differences between irradiated vs. mitomycin C‐treated stimulators
Authors: Webb Susan R. , Li Jane Hu , Wilson Darcy B. , Sprent Jonathan 
Published: February 2007

AbstractTo investigate whether small B cells can stimulate mixed lymphocyte reactions (MLR), highly purified populations of large vs. small B cell fractions were tested for their capacity to evoke MLR across Mls vs. H‐2 barriers. Large B cell fractions stimulated high MLR to Mls and H‐2 determinants, irrespective of whether the stimulators were exposed to irradiation or pretreated with mitomycin C. In accord with the findings of others, irradiated small B cell fractions proved to be very poor stimulators of MLR. Significantly, however, mitomycin C‐treated small B cell fractions elicited high MLR, particularly to Mls determinants.The finding that small B cell fractions treated with irradiation are poor stimulators of T cells correlates with the known radiosensitivity of B cells. In this respect, the widely held view that small B cells do not have antigen‐presenting cell (APC) function rests largely on studies with irradiated B cells. The present finding that T cells respond well to small B cells treated with mitomycin C, however, indicates that small B cell fractions do have APC function. Whether the APC function of small B cells reflects a response to resting B cells per se rather than to cells undergoing activation in vitro, however, remains to be ascertained.
Lectin separation of nonlymphoid suppressor cells induced by total lymphoid irradiation
Authors: Morecki Shoshana , Weigensberg Marilyn , Slavin Shimon 
Published: February 2007

AbstractSuppression of the mixed lymphocyte reaction (MLR) exerted by splenocytes derived from mice treated with fractionated total lymphoid irradiation (TLI, 200 rds × 8) was analyzed by various criteria in order to characterize the phenotype of the cell type(s) responsible for suppression. TLI‐induced suppressor cells could not be eliminated by removal of cells bearing surface immunoglobulin, Thy‐1, Lyt‐2 and TL, and thus could not be ascribed to lymphocytes of the B or T cell lineage. Suppressor cells were large, and nonadherent to nylon wool, Sephadex G‐10 and plastic surfaces. Suppressor activity of TLI splenocytes was predominantly located in fractions of cells bearing receptors for soybean agglutinin (SBA), peanut agglutinin (PNA) or both lectins. SBA+, PNA+′, sequentially agglutinated (SBA followed by PNA) SBA+PNA+ and (PNA followed by SBA) PNA+SBA+ suppressor cells were radioresistant upon exposure to 1000 rds in vitro. Cells bearing the receptor for PNA but lacking that for SBA (PNA+SBA−) had sharply reduced suppressor activity. However, a radiosensitive PNA− suppressor cell subset was also documented in the spleen of TLI‐treated mice. Thus, suppressor cells could best be physically separated from nonsuppressors by the SBA lectin. SBA+ suppressor cells were found, by scatter analysis, to include the population of large cells characteristic of TLI splenocytes, whereas SBA− cells were much smaller and almost exclusively devoid of suppressive capacity. The PNA receptor was found to further dissect the SBA+ suppressor cells into two distinct subpopu‐lations: radioresistant SBA+PNA+ cells and radiosensitive SBA+PNA− cells. In summary, we suggest here the presence of at least two suppressive populations induced by TLI: (a) radioresistant SBA+, PNA+, SBA+PNA+ or PNA+SBA+ cells, and (b) radiosensitive PNA− and SBA+PNA− cells. Similar subsets of MLR suppressor cells can be isolated from normal bone marrow cells and splenocytes of nude mice, suggesting that suppression is mediated by large, immature, nonlymphoid cells which might migrate from shielded bone marrow compartments into the spleen of TLI‐treated mice.
Function of alloproliferative T lymphocyte clones correlates better with their class II recognitive specificity than with their cell surface phenotype
Authors: Pawelec Graham , Schneider E. Marion , Wernet Peter 
Published: February 2007

AbstractAlloproliferative primed lymphocyte typing (PLT) clones recognizing determinants associated with HLA‐DR/Dw, SB, MB, or novel “SB‐like” gene products were screened for their ability to suppress lymphoproliferative responses in primary and secondary mixed lymphocyte cultures (MLC), and for their surface marker pheno‐types. Two nonsuppressive HLA‐D specific PLT clones were OKT4−, OKT+ whereas all others possessed an OKT4+, OKT8−, Leu‐8− phenotype. All clones secreted interleukin 2 (IL2) after specific stimulation. The eight PLT clones specific for “SB‐like” antigens strongly suppressed MLC, whereas only one of 35 DR/Dw‐specific, and none of 20 SB‐specific PLT clones did so. Suppressive activity of such PLT clones was not restricted by major histocompatibility complex products, was radioresistant (20 Gy), and was not caused by absorption of IL2 or by cytotoxicity of the cloned cells. Suppressive clones exerted their effects directly on proliferating T cells, as assessed by their ability to prevent growth of cloned PLT cells stimulated by B cell lines, and their ability to block primary MLC even when added 96 h after the start of the 144‐h culture. Culture supernatants from suppressive, but not from nonsuppressive, PLT clones also strongly and nonspecifically inhibited lymphoproliferative responses. The suppressive factor(s) was not dialyzable, not sensitive to pH 2 or heat treatment and not cytotoxic. Thus, all T cell clones proliferating against novel “SB‐like” but not SB antigens, as well as rare clones specific for D region determinants, possess powerful nonspecific suppressive activities dissociated from their “helper‐related” OKT4+, OKT8‐, Leu8−, IL2‐secreting phenotypes.
Tumor promoter phorbol esters induce unresponsiveness to antigen and expression of interleukin 2 receptor on T cells
Authors: Ando Istvan , Hariri Gita , Wallace Diana , Beverley Peter 
Published: February 2007

AbstractThe tumor promoter 12‐O‐tetradecanoylphorbol l3‐acetate induces the expression of the interleukin 2 receptor and the disappearance of the T3 complex in a T cell hyb‐ridoma, T cell clones, thymic and peripheral T cells and T cell tumors. These changes are accompanied by an increased sensitivity to interleukin 2 and antigen‐specific unresponsiveness in T cell clones.
Inhibition of hapten‐specific cytotoxic T cell recognition by monoclonal anti‐hapten antibodies
Authors: Pircher Hanspeter , Zinkernagel Rolf M. , Hengartner Hans 
Published: February 2007

AbstractThe T cell‐mediated Cytotoxic response against autologous cells modified with the sulfhydryl reagent I‐AED (N‐iodoacetyl‐N′‐(5‐sulfonic‐l‐naphthyl) ethylene diamine) is hapten specific and H‐2 restricted (Levy, R. B., Shearer, G. M., Richardson, J. C. and Henkart, P. A., J. Immunol. 1981. 127: 523). We have produced a monoclonal antibody (V‐6‐3, IgM) which binds to AED‐modified cells and proteins. Competition experiments by free hapten indicated that the binding was AED specific. The effect of the mAb on AED‐specific cytotoxic T cell recognition at the effector and induction stage has been examined. Anti‐AED mAb inhibited the cell‐mediated lysis of some but not all AED‐specific, H‐2b‐restricted long‐term cytotoxic T cell clones and of bulk‐cultured C57BL/6 anti‐AED‐self effector cells. This blocking was not due to nonspecific agglutination of targets since lysis of AED‐modified target cells by alloreactive effector cells was not affected by this mAb under comparable conditions. Furthermore anti‐AED mAb specifically inhibited the antigen‐induced proliferation of AED‐specific long‐term cytotoxic T cell clones and the generation of AED‐specific cytotoxic effector cells in secondary cultures. This monoclonal anti‐AED antibody bound to cells modified by the recently described aminoreactive reagent AED‐NH2 (Takai, Y., Mizuochi, H., Fujiwava, H. and Hamaoka, T., J. Immunol. 1984. 132: 57); these same target cells were, however, not lysed by AED‐SH‐specific cytotoxic T cell clones.
Isotypically restricted activation of B lymphocytes by lactic dehydrogenase virus
Authors: Coutelier Jean‐Paul , Van Snick Jacques 
Published: February 2007

AbstractLactic dehydrogenase elevating virus (LDV) was found to selectively stimulate IgG2a synthesis in infected mice. Within one week after infection, the production of IgG2a increased nearly 50‐fold whereas that of IgM, IgA, IgGl and IgG3 remained virtually unchanged. IgG2b synthesis was also enhanced but to a lesser extent. Several observations suggested that this stimulation of IgG2 production resulted from a polyclonal B cell activation: (a) the isoelectric focusing patterns of IgG2a, before and after LDV infection were exactly the same, (b) the frequency of clones with anti‐LDV activity in hybridoma collections derived from infected mice was extremely low (less than 4/ 1000) and (c) the proliferative response elicited by LDV in unsensitized animals was comparable with that induced by lipopolysaccharide. The effect of LDV on immunoglobulin synthesis was drastically reduced in nude mice but was not affected by the X‐linked B lymphocyte defect of animals carrying the xid mutation.
Antigen‐specific suppression of anti‐influenza antibody production in man. Possible role of a membrane‐antigen complex
Authors: McCaughan Geoffrey W. , Brown Marion H. , Basten Antons 
Published: February 2007

AbstractE rosette‐forming (E′) cells from human secondary lymphoid tissue were incubated with high dose influenza A virus (Mem‐Bel) in an attempt to generate antigen‐specific suppressor T cells. Suppression was assayed by transferring the antigen‐pulsed E+ cells into effector cultures consisting of E+ and E− cells stimulated with immunogenic amounts of either the inducing virus (Mem‐Bel) or the non‐cross‐reacting influenza B virus (B/HK). The transfer resulted in marked inhibition of IgG, IgA and IgM antibody production to Mem‐Be1 but not to the control antigen, B/HK virus. The suppres‐ sive effect was specific at the level of induction as well as expression since E+ cells exposed to high dose Mem‐Be1 could provide help to an effector culture containing E− cells and optimal dose of B/HK virus. However, metabolically active cells did not appear to be required for suppression. Thus, it could be elicited (a) after only 15 min incubation of E+ cells with high‐dose virus and (b) by E+ cells exposed to irradiation, incubated in the presence of metabolic inhibitors, or disrupted by repeated freeze thawing. In contrast, treatment of E+ cells with pronase reversed the suppressive effect. Interestingly, virus heated to 70 oC failed to induce suppression, while retailing the ability to elicit a normal helper response.Suppression induced by exposure to standard amounts of high‐dose antigen was medi‐ ated by T cells of both helperiinducer (Leu‐3a+) and suppressoricytotoxic subsets (Leu‐2a+), but not by B cells. Two groups of observations pointed to the B cell as the target of suppression. First, suppression could still be transferred to effector cultures in which helper T cells had been replaced by T cell‐replacing factor or suppressor T cells removed by irradiation. Second, significant inhibition of antibody production was obtained when the transfer of antigen‐pulsed E+ cells was delayed for up to 120 h after initiation of the effector culture. Taken together the results suggest that suppression in this system is due to the formation of an antigen bridge between specific receptor sites on the T cell membrane and the target. Although not dependent on triggering of metabolically active suppressor T cells the phenomenon highlights the need for care in interpreting the mechanism of suppression by high‐dose antigen and could, in addition, represent a biologically important control mechanism capable of rapid inhibition of effector T cells and B cells in sites of high antigen concentration.
Phorbol ester‐induced expression and function of the interleukin 2 receptor in human B lymphocytes
Authors: Ando Istvan , Crawford Dorothy H. , Kissonerghis Maija A. , Owen Michael J. , Beverley Peter C. L. 
Published: February 2007

AbstractThe expression of the interleukin 2 receptor (Tac) on normal B cells and Epstein‐Barr virus‐transformed lymphoblastoid B cell lines is induced by the tumor promoter 12‐O‐ tetradecanoyl‐phorbol‐13‐acetate (TPA). The receptor on B cells is indistinguishable from that on T cells by serological and biochemical analysis. It is functionally active so that TPA‐induced B cells respond to interleukin 2 by increased DNA synthesis. These results suggest that the expression of Tac is not exclusively restricted to T cells and that interleukin 2 may play a role in B cell differentiation.