bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of specific suppressor T cells in newborn responder mice by the terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10 (GAT)
Authors: Debre P.
Published: February 2007

The effects of immunization with the terpolymer of L‐glutamic acid60‐L‐alanine40‐L‐tyrosine10 (GAT), the copolymers of L‐glutamic acid60‐L‐alanine40 (GA) and of L‐glutamic acid50‐L‐tyrosine50 (GT), were compared in adult and newborn BALB/c and BALB.B mice. As expected, BALB/c (H‐2d) and BALB.B (H‐2b) adult mice were responders to GAT and GA and nonresponders to GT, which induced suppressor T cells in BALB/c but not in BALB.B mice. In contrast, newborn mice expressed different phenotypes. Two‐week‐old mice developed responses to GAT, GA and GT‐complexed methylated bovine serum albumin, but immunization at birth with these copolymers induced a cross‐reactive tolerance in both strains. Neonatal GAT tolerance could be transferred in adult and involved suppressor T cells in the two inbred strains, whereas the GT‐specific immune suppression was not demonstrable in newborn BALB/c mice. The significance of these data to our understanding of the regulation of specific immune response and tolerance is discussed.
Studies on induction and control of cell‐mediated autoimmunity II. Prevention of induction and activity of autoreactive T cells by suppressor cells and by a suppressive serum factor
Authors: L'age‐Stehr Johanna , Diamantstein T.
Published: February 2007

Autoreactive T lymphocytes (T‐ARC) can be detected in the spleen of mice treated with a single dose of cyclophosphamide (CY) (125 mg/kg), a peak occurring 6 days after CY injection. Eight days after CY treatment, the mice develop a specific anergic state. This anergic state can be transferred to normal syngeneic animals by either splenic nylon wool‐nonadherent lymphocytes (suppressor cells, S‐ARC) or by the serum of anergic mice, implying the development of an active suppressive mechanism due to CY treatment. Precursors of both potentially T‐ARC as well as S‐ARC coexist in the spleen of normal animals. Precursors of S‐ARC present in the spleen and in the thymus of normal animals are sensitive to CY. However, committed S‐ARC obtained from anergic mice are resistant to CY. Committed S‐ARC as well as their precursors prevent induction of T‐ARC. Committed S‐ARC counteract expression of committed T‐ARC activity, whereas precursors of S‐ARC fail to do so.

The autoimmune phenomenon described here represents an in vivo animal model system for induction of T‐ARC and for the control mechanism which normally prevents induction and/or expression of cell‐mediated autoreactivity by specific suppressor cells and by suppressive factors.
Characterization of natural killer (NK) cells and killer (K) cells in human blood: Discrimination between NK and K cell activities
Authors: Bolhuis R. L. H. , Schuit H. R. E. , Nooyen A. M. , Ronteltap C. P. M.
Published: February 2007

Cell suspensions enriched and depleted for rosette‐forming cells with sheep red blood cells (E‐RFC) and depleted for RFC with antibody complexes were prepared. The isolated fractions were characterized by cell surface marker analysis and tested for their natural killer (NK) and killer (K) cell activity against K‐562 cells and IgG‐coated P‐815 cells, growing in suspension, and against a number of monolayer tumor cell lines. It was found that the NK cells most likely belong to the T cell lymphocyte subpopulation. Furthermore, this study indicates that several subpopulations exist, e.g. NK cells that have no IgG Fc receptor (FcR) on their surface and NK cells that bear IgG FcR, indicating that for a proportion of NK cells the IgG FcR is not involved in the NK lytic process and hence antibody‐independent. Moreover, monocytes and B lymphocytes appear not to be directly involved in the NK cell lytic process.

Furthermore, cell separation procedures were used to obtain cell suspensions either bearing IgG FcR or lacking IgG FcR. Cells bearing IgG FcR were isolated in such a way that they lost their IgG FcR by shedding, as a result of the separation procedure. Again, all fractions were simultaneously characterized by cell surface marker analysis and tested for their NK and K cell lytic activity. The effect of immune complexes on the NK and K cell lytic activities was investigated. The data indicate that the IgG FcR is not involved in the NK lytic mechanism, although this receptor may be present on the NK cell. Moreover, prolonged culturing of lymphocytes increases and/or induces NK cell lytic activity.
Some chronic lymphocytic leukemia cells bearing surface immunoglobulins share determinants with T cells
Authors: Boumsell Laurence , Bernard A. , Lepage Virginia , Degos L. , Lemerle J. , Dausset J.
Published: February 2007

One set of antigens is common to some chronic lymphocytic leukemia (CLL) cells bearing surface immunoglobulins (Ig) and normal T cells. Proliferating cells from thirty‐eight patients were studied with four antisera recognizing normal human T but not B cells. These antisera were raised in rabbits against (a) Sezary cells, (b) blood lymphocytes from a patient with sex‐linked agammaglobulinemia, (c) T lymphoblasts and (d) thymus cells. In four CLL cases, the cells expressed the receptor for sheep erythrocytes and lacked surface Ig. Cells from thirty‐four CLL cases bore monoclonal surface Ig and did not bind sheep erythrocytes. Twelve out of these thirty‐four cases of CLL had cells which were lysed by one or, more frequently, by the four anti‐human T cell xenoantisera. By absorption experiments, one set of at least three antigens common to the cells of some of these CLL and T cells was defined. Depending on the patient, the cells can either carry one, some or all of the antigens of this set. However, it was also demonstrated by absorption that these cells lacked antigens particular to the T cell lineage, while the cells from T CLL cases carried both sets of antigens.
The clonal analysis of cytotoxic lymphocytes against 2,4,6‐trinitrophenyl (TNP)‐modified cells
Authors: Ching Lai‐Ming , Marbrook John
Published: February 2007

The frequency and specificity of clones of cytotoxic lymphocytes (CL) produced when (CBA × C57BL)F1 spleen cell populations were cultured with 2,4,6‐trinitrophenyl (TNP)‐modified syngeneic F1 cells, was examined. The frequency of clones which lysed F1‐TNP targets was 1/3.3 × 104 spleen cells, and the frequency of clones which lysed the modified parental cells, CBA‐TNP and C57BL‐TNP was 1/6.7 × 104 and 1/2.9 × 105 spleen cells, respectively. Using a clonal analysis of the specificity of the CL, it was shown that the majority of the clones of CL which lysed the two modified parental targets, were specific for one or the other of the targets. Activity against modified allogeneic DBA/2‐TNP targets was also detected. The activity against DBA/2‐TNP targets was due mainly to clones of CL which were specific for DBA/2‐TNP targets. Only a minor part of the activity was due to clones which were cross‐reactive for both F1‐TNP and DBA/2‐TNP target cells.
Interaction of anti‐staphylococcal protein A antisera with Fc receptor‐bearing human normal lymphocytes
Authors: Biguzzi Sergio
Published: February 2007

Staphylococcal protein A (SpA) is known to bind the Fc region of IgG of most mammalians and to possess biologic activity both in vivo and in vitro, where it acts as a lymphocyte polyclonal mitogen. Its binding to the Feγ portion bears many features of the antibody‐antigen interaction, such as the dissociation constant, lattice formation, and complement activation. Moreover, SpA seems to compete with membrane Fc receptors for IgG so that the possibility of an interaction with the same CH domain(s) of IgG can be considered. In the present study, evidence is given that anti‐SpA anti‐sera obtained from chickens and rabbits are able to inhibit EA rosette formation by normal human lymphocytes and that they are able to recognize, with immunofluorescent staining, a subpopulation of normal human peripheral blood lymphocytes (PBL) that closely resembles that of EA rosette‐forming cells (RFC). Moreover, the depletion of EA RFC by means of a single gradient centrifugation is accomplished by the parallel depletion of PBL stainable by anti‐SpA antisera. The relevance of these results in the hypothesis of a similarity between the combining sites of SpA and membrane Fc receptor(s) for IgG is discussed.
IgA‐containing plasma cells in the lamina propria of the gut: failure of a thoracic duct fistula to deplete the numbers in rat small intestine
Authors: Mayrhofer G. , Fisher R.
Published: February 2007

The quantitative importance of the traffic of large lymphocytes through the thoracic duct to the maintenance of the IgA‐containing plasma cell population of the lamina propria of the gut was examined by draining the thoracic duct for periods of time up to 10 days. Contrary to the expectation that IgA‐secreting plasma cell numbers in the small intestine would decline exponentially with a half‐time of approximately 5 days, the numbers of cells remained relatively constant after an initial decline in the first 4 days of lymphatic diversion. Results of in vivo pulse labeling with tritiated thymidine suggest that plasma cell numers are maintained by cell proliferation within the intestinal lamina propria, and that this is a compensatory mechanism brought into play by removal of the normal supply of precursors from the thoracic duct. The compensatory local recruitment of dividing plasma cell precursors principally involves those committed to IgA synthesis. It is suggested that thoracic duct lymph diversion calls into play a local mechanism to make up the deficit of plasma cell precursors lost in the lymph. This may be an accentuation of normal regulation of IgA synthesis in the lamina propria, and suggests that the homing of thoracic duct large lymphocytes is not the only source of renewal of gut plasma cells.
Anti‐V region framework antibodies affect the ligand binding of VL dimer
Authors: Ben‐Neriah Yinon , Givol David , Gavish Moshe
Published: February 2007

The effect of antibodies to the light chain variable region (VL) of protein MOPC‐315 (a, Λ2), on the binding of hapten by VL315 dimer or Fv315 (VL + VH) was studied by equilibrium dialysis. Anti‐VL did not change the binding properties of Fv but affected the binding properties of VL dimer. At pH 5, the binding properties of VL in the presence or absence of anti‐VL were the same, whereas at pH 8, anti‐VL reduced the number of ligands bound to VL from two to one. It has previously been shown that VLdimer binds one ligand at pH 5 and two ligands at pH 8, and that VL conformation at pH 5 is tighter. Hence, our results suggest that anti‐VL tightens the conformation of VL dimer at pH 8.0 such that it can bind only one ligend. Since Fv is not affected by anti‐VL, the results indicate that a combining site made of two identical chains (VLdimer) can undergo a conformational change upon interaction with its antibody. Such conformational change can indirectly affect the binding properties.
Regulation of delayed‐type hypersensitivity. IV. Antigen‐specific suppressor cells for delayed‐type hypersensitivity induced by lipopolysaccharide and sheep erythrocytes in mice
Authors: Gill Harvinda K. , Liew Foo Y.
Published: February 2007

Mice injected subcutaneous with 1 × 108 sheep red blood cells (SRBC) developed high levels of delayed‐type hypersensitivity (DTH) to SRBC 4–8 days after injection. Such DTH was suppressed when 100 μg lip polysaccharide (LPS) was injected intravenously 1–2 days before or at the time of SRBC injection. This suppression of DTH was transferable by spleen, lymph node, thymus and bone marrow cells to sensitize or normal syngeneic recipients, but could not be transferred by serum. Suppressor cells were not induced by LPS alone or SRBC alone, and they were antigen‐specific since DTH to chicken red blood cells was not affected. The suppressor cells appeared in the spleen in optimum number 3–4 days after induction. They were theta‐negative and Ig‐positive as judged by antiserum plus complement treatment and by Ig rosette separation. Attempts to obtain soluble suppressor factor from the suppressor cells by sanitation or in vitro incubation were unsuccessful. Mitomycin C treatment of the suppressor cells completely abolished the suppressor activity. Thus, LPS, in conjunction with antigen, appears to induce a population of specific suppressor B cells which are capable of regulating T cell function.
Mycoplasma neurolyticum: a potent mitogen for rat B lymphocytes
Authors: Naot Yehudith , Merchav Shoshana , Ginsburg Haim
Published: February 2007

A mitogen prepared from Mycoplasma neurolyticum has been demonstrated to induce extensive transformation of in vitro cultured rat B lymphocytes. The data summarized in this report show that rat thymus cells as well as hydrocortisone‐resistant thymocytes were not activated by this mitogenic agent. On the other hand, spleen cells obtained from thymectomized, lethally irradiated and bone marrow‐reconstituted rats were extensively activated by M. neurolyticum. Furthermore, M. neurolyticum was shown to induce the development of antibody‐producing cells, as attested by the appearance of direct plaque‐forming cells against sheep red blood cells and trinitrophenylated sheep red blood cells in spleen cell cultures exposed to this mitogen. It was also demonstrated that stimulation of rat lymphocytes by this mitogen was inhibited by anti‐rat immunoglobulin antibodies.

In view of these data, it was suggested that M. neurolyticum, which activates mouse B lymphocytes, is a potent mitogen for rat B lymphocytes as well. This mitogen is a significantly more powerful mitogen for rat B lymphocytes than any other known mitogens. The availability of such mitogenic material in the rat system will enable studies on control mechanisms of action and differentiation of rat B lymphocytes.
Fine specificity of cytotoxic T lymphocytes: C57BL effector cells induced by autologous cells modified with hapten (4‐hydroxy‐3‐nitro‐phenyl)acetyl (NIP) are not heteroclitic
Authors: Andó Istvan , Kisielow Pawel
Published: February 2007

Cytotoxic T lymphocytes (CTL) were generated to syngeneic cells derivatized with serologically cross‐reactive compounds (4‐hydroxy‐3‐nitro‐phenyl)acetyl (NP) and (4‐hydroxy‐5‐iodo‐3‐nitro‐phenyl)acetyl (NIP) in order to investigate the possible role of a heteroclytic T and B cell receptor marker (U. Krawinkel et al., Eur. J. Immunol. 1977. 7: 566) in CTL‐target cell interaction. The cytotoxic cells of both BALB/c and C57BL/10 (B 10) origin react specifically with target cells of the inducer type; no heteroclicity of the overall cytotoxic response can be observed by CTL of B 10 origin. The results suggest that in this system, the specificity of CTL is determined by a receptor with a variable region different from that of the isolated NP‐specific antigen‐ binding T cell receptor material.
Relationship between histocompatibility antigens, other surface determinants and the IgE receptor on rat mast cells
Authors: Mossmann Horst , Schmitz Balthasar , Lauer Wolfgang , Staufier Uta , Gehrung Marina , Günther Eberhard , Hammer Dietrich K.
Published: February 2007

Rat alloantibodies recognizing classical transplantation antigens (CTA) or non‐H‐1 determinants were able to compete effectively with monomeric IgE or IgG‐coated sheep erythrocytes for receptor sites on the rat mast cell surface. Inhibitory capacity, however, was entirely confined to anti‐CTA antibodies of the IgG2a subclass, whereas IgG1 antibodies lacked this ability.

Analogously, F(ab')2 fragments of anti‐CTA antibody consistently failed to affect IgE binding, but exposure of cell‐bound F(ab′)2 to anti‐rat IgG restored its inhibitory capacity. From these results it was concluded that receptor sites recognizing the Fc portion of the anti‐CTA molecule are involved in the inhibition process.

Based on a cytotoxicity assay and on comparative absorption studies on alloantisera, the existence and relative amount of CTA and I region‐associated antigens on purified rat mast cells and lymph node cells were analyzed. Whereas the CTA concentration per unit surface area on both cell types was very similar, rat mast cells consistently lacked Ia antigens.
Antibody‐dependent cellular cytotoxicity against tumor cells. I. Cultivated bone marrow‐derived macrophages kill tumor targets
Authors: Lohmann‐Matthes Marie‐Luise , Domzig Wolfgang , Taskov Hristo
Published: February 2007

Mouse bone marrow cells are cultivated in a liquid culture system in the presence of fibroblast conditioned medium. Under these conditions, proliferation of macrophage and granulocyte precursor cells is induced. Cells of a 5‐day‐old culture are shown to act as cytotoxic effector cells against tumor targets such as P815, E14, YAC and L5178 Y. The effector cell is of macrophage origin since it is susceptible to treatment with the alloantiserum Mph‐1.2 plus complement. The kinetics of the reaction resembles the kinetics for killer (K) lymphocyte lysis. In contrast to bone marrow cells, peritoneal macrophages do not show cytotoxic activity against antibody‐coated tumor targets although they are susceptible to activation to cytotoxicity by lymphokines. The possible relationship of bone marrow effector cells and K lymphocytes is discussed.
In vitro induction of delayed‐type hypersensitivity
Authors: Bretscher Peter A.
Published: February 2007

Murine spleen cells, cultured in vitro for 6 days in the presence of high concentrations of burro erythrocytes (BRBC), are sensitized to exhibit delayed‐type hypersensitivity (DTH) specific for this antigen. Such cells, on being injected with antigen into the footpads of normal mice, cause a 24‐h swelling reaction. This activity of the cultured cells requires the presence of BRBC both during the in vitro incubation and in the footpad. The activity of the sensitized cells in causing swelling is sensitive to anti‐Thy‐1 antibody and complement, and the kinetics of the swelling reaction are characteristic of a DTH response. In vivo low‐dose priming of the spleen cell donors considerably enhances the ability of the cultured cells to cause swelling. This system provides a means of studying the regulation of the induction of DTH in vitro.
Induction Of Thymocytotoxic Autoantibodies After Injection of Bacterial lipopolysaccharides in Mice
Authors: Izui Shozo , Kobayakawa Takatoshi , Louis Jacques , Lambert Paul‐Henri
Published: February 2007

The injection of bacterial lipopolysaccharides (Salmonella typhimurium and Escherichia coli LPS) has been shown to induce thymocytotoxic autoantibodies in various strains of mice (C57BL/6, BALB/c, DBA/2, AKR, A/J and C3HeB/FeJ). Titers up to 1:16 were observed. Such antibodies did not develop in C3H/HeJ mice which are low responders to LPS. The thymocytotoxic antibodies had the following characteristics: (a) 2‐mercaptoethanol sensitivity, (b) optimal reactivity at 4 °C, (c) cytotoxicity for autologous and syngeneic thymocytes but not for spleen cells. The cytotoxicity decreased after absorption with thymocytes, spleen cells or brain tissue but not with kidney or liver homogenates. These LPS‐induced thymocytotoxic antibodies were similar to the natural thymocytotoxic antibody occurring in NZB mice.
Lysolecithin analogs as adjuvants in delayed‐type hypersensitivity in mice. II. Studies on the mode of action
Authors: Arnold Bernd , Staber Frit Z. G. , Miller Jacques F. A. P.
Published: February 2007

Lysolecithin analogs (LLA) possess adjuvant activity in delayed‐type hypersensitivity (DTH). To elucidate their mode of action, we studied the influence of LLA on the recruitment of hemopoietic progenitor cells and on the induction and transfer of DTH. Whereas the number and composition of colony‐forming cells (CFC) in the bone marrow remained unaltered in LLA‐treated mice, the number of CFC in the spleen was augmented severalfold, and the content of macrophage progenitors was remarkably increased. DTH was induced with macrophages from peritoneal cells (PC) pulsed with keyhole limpet hemocyanin (KLH). A more marked DTH response was obtained with KLH‐pulsed PC from LLA‐treated mice than from mice given phosphate‐buffered saline (PBS). On the other hand, there was no difference in the DTH response following adoptive transfer of sensitized cells to naive mice pretreated either with PBS or LLA. It is concluded that the adjuvant effect of LLA can be accounted for partly in terms of their effects on macrophage progenitors and partly in terms of a more effective T cell activation by antigens associated with LLA‐derived macrophages.
Platelet‐activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes
Authors: Mencia‐Huerta Jean Michel , Benveniste Jacques
Published: February 2007

Platelet‐activating factor (PAF) is a phospholipid mediator of anaphylaxis, released from basophils of several mammalian species, that aggregates platelets and releases their vasoactive amines. The ionophore A23 187 induced the release of PAF from rat and mouse peritoneal cells, a mixed cell population that was fractionated using 5–15 % Ficoll gradients and adherence to plastic petri dishes. PAF was associated with large, acid phosphatase‐containing, adherent mononuclear cells. Mastocytes did not release PAF but released histamine by the action of ionophore or 48/80; they could not be held responsible for inactivation of PAF or inhibition of the PAF‐induced platelet aggregation.

These data indicate that, besides blood basophils, peritoneal macrophages are a likely source for PAF, a result that adds a new important function to the macrophage: aggregation of platelets and liberation of their inflammatory and vasoactive substances.
Suppressor cells and immunodeficiency in (NZB × NZW)F1 hybrid mice
Authors: Michalski Joseph P. , McCombs Candace C. , Talal Norman
Published: February 2007

Old (15–20 month) male (NZB × NZW)F1 (B/W) mice have severely impaired spleen cell reactivity to phytohemagglutinin (PHA), a mitogen which stimulates mainly T lymphocytes. Spleen cells from old mice markedly suppressed the PHA response of splenocytes from young (3–4 month) B/W males. Similar suppressor activity was not present in the spleens of old mice of four nonautoimmune strains.

The suppressor activity of old B/W spleen cells was mediated by a nonphagocytic, radioresistant, mononuclear leukocyte. Although this cell was eluted in the “T lymphocyte” fraction of nylon wool columns, it was not sensitive to treatment with anti‐Thy‐1 antiserum and complement. Suppressor activity was lost after 18 h incubation at 37 °C in tissue culture medium. Supernatants of these overnight cultures had no suppressive effect on fresh young B/W spleen cells.

Old B/W spleen cells suppressed PHA reactivity more than concanavalin A or lipopolysaccharide reactivity. Kinetic studies demonstrated an increasing suppression with time over 72 h of culture. This study demonstrates that the severely impaired PHA reactivity of old B/W mice is mediated, at least in part, by active suppression.
Inhibition of T cell‐mediated cytolysis by 2‐deoxy‐D‐glucose: dissociation of the inhibitory effect from glycoprotein synthesis
Authors: MacDonald H. Robson , Cerottini Jean‐Charles
Published: February 2007

Previous studies have established that T cell‐mediated cytolysis can be reversibly inhibited by the hexose analogue 2‐deoxy‐D‐glucose (2‐DG) by a mechanism which is apparently unrelated to energy depletion. The possibility that the inhibitory effect of 2‐DG on cytolysis was linked to its known inhibitory effect on glycoprotein synthesis was therefore investigated. In contrast to the results obtained with 2‐DG, no inhibition of cytolysis was observed in the presence of tunicamycin, a potent and specific inhibitor of lipid carrier‐dependent protein glycosylation. Furthermore, populations of cytolytic cells which had been pretreated with doses of tunicamycin sufficient to block the incorporation of mannose (or 2‐DG) into glycoproteins were still fully susceptible to inhibition by 2‐DG. Other known inhibitors of viral protein glycosylation, such as glucosamine and galactosamine, inhibited cytolysis only weakly under conditions where 2‐DG was highly effective. Kinetic studies revealed that the inhibitory effect of 2‐DG on cytolysis could be reversed within minutes by the addition of exogenous glucose. Furthermore, suggestive evidence was obtained that inhibition of cytolysis by 2‐DG was linked to a parallel inhibition of effector: target cell binding. Taken together, these results strongly suggest that the inhibitory effect of 2‐DG on cytolysis can be dissociated from its effect on protein glycosylation. An alternative mechanism of action of 2‐DG is suggested.
Investigation of the human macrophage II. The in vitro cytotoxicity of macrophages
Authors: Chang Yu‐Hui , Yao Chin‐Sheng
Published: February 2007

Macrophage‐mediated cytotoxicity in vitro was studied by a tritiated thymidine incorporation inhibition assay as well as by microscopic examination and optical transmittance determination. It was found that macrophages from patients with malignant diseases showed cytotoxic effects on two malignant human cell lines. The cytotoxic activity was more marked in patients who were clinically tumor‐free. Some patients with benign diseases and normal subjects also exhibited cytotoxic macrophages. Macrophage‐mediated cytotoxicity (MMC) was thus nonspecific in nature. Cell‐free exudate from cancer patients did not influence MMC appreciably. The experimental methods and the possible significance of MMC are discussed.
Studies on T lymphocyte activation II. The target cells for concanavalin A‐induced growth factors
Authors: Coutinho Antonio , Larsson Eva‐Lotta , Grönvik Kjell‐Olov , Andersson Jan
Published: February 2007

Growth factors contained in Con A(concanavalin A)‐conditioned media (CM) maintain exponential growth in T cell blasts derived from mitogen stimulation of spleen cells with Con A, phytohemagglutinin, lentil lectin and pokeweed mitogen (PWM), as well as from mixed lymphocyte reactions to H‐2 D or I‐E and I‐C‐encoded determinants and from non‐H‐2 Mls locus‐controlled reactions. Such growth factors are strictly T cell blast‐specific, inasmuch as they do not stimulate resting, small T or B lymphocytes nor B cell blasts generated by lipopolysaccharide or lipoprotein activation. The responsiveness of T cell blasts to CM appears to be the result of the availability on the cell surface of an acceptor site for growth factors which is not expressed in resting cells, because T cell blasts, but not small spleen cells, absorb out the growth‐promoting activity contained in CM. Furthermore, lectins such as Con A and PWM interfere with the blast surface membrane in such a way that they inhibit the response to growth factors. Finally, there is no detectable allotypic or isotypic restriction in the activity of Con A‐CM on a variety of target T cell blasts.
Restoration by serum thymic factor of colony‐forming unit (CFU‐S) entry into DNA synthesis in thymectomized mice after T‐dependent antigen treatment
Authors: Lepault Francoise , Dardenne Mireille , Frindel Emilia
Published: February 2007

Adult thymectomy prevents stimulation of hematopoietic stem cells as measured by colony‐forming units (CFU‐S) if T‐dependent antigens are injected, but not when T‐ independent antigens are used. This can be observed as soon as 10 to 15 days after thymectomy. The serum thymic factor can restore CFU‐S response to T‐dependent antigens in thymectomized mice.
Regulation of tumor growth and antibody clone expression by antigen and anti‐idiotype antibody ligands with specificity for receptor‐binding sites
Authors: Bell Clara , Klein Eva
Published: February 2007

Dextran ligands, modified to increase epitope reactivity with receptors, were more effective in suppressing BALB/c mouse plasmacytomas MOPC 104 E and J‐558, which bind α(1 → 3) dextran and have an idiotype (Id) in common, than autoantibody (Ab) against the Id unique to each of the proteins secreted by the two tumors (the Idl). BALB/c immunized with 104 E myeloma protein and expressing an antibody response to the 104 E Idl exhibited a specific, anti‐104E Idl transplantation resistance to lethal grafts of 104E, but not J‐558, tumors notwithstanding the shared common Id and similar ability to bind a(1 → 3) dextran. This autoantibody did not prevent modulation of the 104 E tumor to variant forms or the growth of the variants. On challenge with a(1 → 3) dextran, the immunized mice expressing the anti‐104E Idl responses failed to express the 104E Idl‐like antibody clone present in the normal, anti‐α(1 → 3) dextran antibody repertoire. Passive, iso‐anti‐104E Idl antibody had a transitory suppressive effect on the normal, 104E Idl‐like antibody clone but failed to circumvent 104 E tumor growth. It is apparent that the greater effectiveness of ligands strongly reactive in a nonphysiological manner with the tumor receptors lies in the stabilization of the tumor load without inducing variant escape or a disturbance of the immune network, and that receptor expression and malignancy state are not necessarily co‐extensive functions.
A rosette assay for the determination of C 1 q receptor‐bearing cells
Authors: Gabay Yvette , Perlmann Hedvig , Perlmann Peter , Sobel Alain T.
Published: February 2007

A rosette assay for the identification of cells with receptors for C 1q is described. Glutaraldehyde‐treated bovine erythrocytes bound C 1q specifically, and the reagent thus prepared provided a valid indicator for rosette formation mediated by C 1 q receptors. The presence of these receptors on the membrane of a subset of human peripheral lymphocytes (mainly non‐T cells) and on B‐derived lymphoblastoid cells was confirmed. Rosette formation was dependent on the number of C 1 q molecules bound per indicator cell and was specifically inhibited by soluble native C 1 q and pepsin‐resistant C 1 q fragments. These data, together with the reduced binding activity of C 1r‐C 1s‐associated C 1q, indicated that the C 1 q binding sites for lymphoid membranes are expressed on the collagen‐like moiety, C 1q rosette formation provided a simple new procedure for fractionation of human lymphocyte populations and separation from phagocytes that do not express receptors for C 1 q.
Recognition of protozoan parasite antigens by murine T lymphocytes I. Induction of specific T lymphocyte‐dependent proliferative response to Leishmania tropica
Authors: Louis Jacques , Moedder Edith , Behin Reza , Engers Howard
Published: February 2007

In order to assess the T cell response to Leishmania tropica in the mouse, a recently described method for the study of T lymphocyte activation by protein antigens has been used. Periaortic and inguinal lymph node cells obtained from mice previously injected at the base of the tail with L. tropica emulsified in complete Freund's adjuvant exhibited intense proliferation when cultured in the presence of parasites, as assessed by measuring of [3H]thymidine incorporation. The response was antigenspecific, was demonstrable from 4 to 75 days after in vivo priming and was T cell‐ dependent by the following criteria, (a) treatment of lymph node cells with rabbit anti‐mouse thymus lymphocyte antigen (MTLA) antiserum and complement greatly reduced the magnitude of the response, (b) purified T cells responded as efficiently as unfractionnated lymph node cells provided irradiated normal peritoneal exudate cells were also added to the culture. Finally, normal peritoneal exudate cells pulsed with L. tropica were able to induce a proliferative response of primed T cells in the absence of extracellular parasites. Therefore, this assay provides a reliable method to measure parasite‐induced T cell proliferation and a convenient system to study the nature of the interactions between antigen‐presenting cells and primed T cells in the induction of a specific T cell response to parasite antigens.
The fine specificity of regulatory T cells IV. Idiotypic complementarity and antigen‐bridging interactions in the anti‐lysozyme response
Authors: Adorini Luciano , Harvey Michael , Sercarz Eli E.
Published: February 2007

The hen egg‐white lysozyme (HEL)‐specific B cells which are activated in response to HEL share a cross‐reactive idiotype as well as submolecular specificity. Helper T cells of two different specificities are implicated in their optimal activation, one recognizing the idiotype and the other, an epitope on the HEL molecule opposite to the one recognized by B cells. Thus, efficient T‐B collaboration involves both idiotypic complementarity and antigen bridging.
Inherited ϰ chain polymorphism in mouse antibodies to phenyloxazolone
Authors: Karjalainen Maus , Hurme Mikko , Mäkelä Olli
Published: February 2007

Mice of several but not all strains produce antibodies of restricted heterogeneity (public idiotype) against hapten 2‐phenyl‐oxazolone (phOx). This public idiotype is controlled by an allotype‐linked gene in crosses between BALB/c and C57BL mice. RF mice do not produce the idiotype although another allotype c strain, DBA/2, does. We studied whether the RF strain is negative for the idiotype because of an unsuitable H chain repertoire or an unsuitable L chain repertoire. Our breeding experiments indicate that the H chain repertoire of RF mice can support synthesis of the public idiotype but the L chain repertoire cannot.
The role of the left end of the H‐2b haplotype in the male‐specific cytotoxic T cell response
Authors: von Boehmer Harald , Turton Kathrin , Haas Werner
Published: February 2007

The male‐specific cytotoxic T cell response was tested in various mouse strains. We found that priming with lo7 nonirradiated or 2 × 107 X‐irradiated cells (2000 Rad) was similarly effective in B 6 mice. We have avoided possible allogeneic effects due to priming F1 hybrids with parental cells and tested all mice after the same time interval for generation of male‐specific cytotoxic T lymphocytes in vitro. Under these conditions, we found an absolute requirement for H‐2b gene products, encoded left of B, in order to see male‐specific responses.
Transferrin can replace serum for in vitro growth of mitogen‐stimulated T lymphocytes
Authors: Dillner‐Centerlind Marie‐Louise , Hammarström Sten , Perlmann Peter
Published: February 2007

Activation of human T cells by mitogens was compared in cultures containing serum, human serum albumin or purified human transferrin as growth support. The mitogenic effect of the lectins leucoagglutinin, concanavalin A and Wistaria floribunda agglutinin was measured as incorporation of [3H]thymidine into the cellular DNA of the lymphocytes. Three different preparations of transferrin were all able to fully substitute serum or serum albumin as growth promotors, when present at concentrations of 10 μg/ml or more. A small contamination of transferrin in the human serum albumin preparations used was shown to be responsible for their growth‐supporting effect, while no need for the presence of albumin itself could be demonstrated.
Restricted expression of a human T cell lineage membrane antigen
Authors: Roberts Marion M. , Greaves Melvyn F.
Published: February 2007

An antiserum raised against human fetal and childhood thymocytes (anti‐Thy) and absorbed with peripheral lymphocytes (tonsil) detected an antigen(s) shared by thymocytes, T cell‐acute leukemias, activated peripheral T cells and a subset of peripheral T cells. The antigen was expressed by the negative circulating T cell subset after mitogen activation of that separated population. The antigen was shown to be separate from the E rosette receptor, another anti‐T cell serum detected antigen, and β2‐microglobulin; its expression was not related to a particular phase of the cell cycle. The results suggest that the antigen is expressed by T cells only under certain maturational and proliferative conditions.
Enrichment of hapten‐specific helper T cells using anti‐immunoglobulin combining site antibodies
Authors: Julius Michael H. , Cosenza Humberto , Augustin Andrei A.
Published: February 2007

Spleen T cells from phosphorylcholine (PC)‐primed BALB/c mice were indirectly stained with affinity column‐purified heterologous rabbit anti‐TEPC 15 (T15) antibodies. These antibodies were shown to be directed towards antigenic determinants in or near the combining site of T15 in that their interaction with the myeloma protein was more than 95% inhibit able by PC. The stained cells were sorted into “bright” and “dull” fractions using a fluorescence‐activated cell sorter. Sorted populations were then assessed for enrichment and depletion of PC‐specific helper activity using an in vivo adoptive transfer assay.

The results indicate that the staining procedure employed enabled the specific enrichment of PC helper T cells and therefore suggest that these T cells bear combining site structures similar to that of the myeloma protein T15.
Absence of an antigen‐specific helper T cell required for the expression of the Tn 15 idiotype in mice treated with anti‐μ antibody
Authors: Bottomly Kim , Janeway Charles A. , Mathieson Bonnie J. , Mosier Donald E.
Published: February 2007

T‐dependent anti‐phosphorylcholine (PC) plaque‐forming cell (PFC) responses were studied in BALB/c mice. Helper T cells derived from normal, carrier‐primed donors induced anti‐PC PFC responses dominated by the T15 idiotype. Helper T cells derived from carrier‐primed mice that had been treated from birth with anti‐μ antibody, so that they were lacking B cells and circulating antibody bearing the T15 idiotype, also provided helper cell function for the anti‐PC antibody response. In contrast to the response induced by helper T cells from normal mice, T helper cells from μ‐suppressed mice induced an anti‐PC antibody response which was mainly non‐ T15 in character. The failure to induce antibody formation by T15+ B cells was not due to suppressor cells but rather to the lack of an Lyt‐1+ helper T cell population which is necessary for predominant T15 production. This latter cell population was shown to be present in carrier‐primed normal but missing or diminished in carrier‐ primed anti‐μ‐treated BALB/c mice. It required carrier priming for the expression of its helper function, but its function did not require the antigen (carrier) to be physically linked to the hapten. From this, we conclude that dominant production of the T15 idiotype involves the synergistic activity of two antigen‐specific helper T cells. The helper cell population which is required for predominant T15 production is greatly diminished in mice treated with anti‐μ antibody from birth. Hence, the production of circulating T15+ antibody induced by environmental antigens or the appearance of T 15‐bearing B cells would appear to be required for the induction of helper T cells which enhance T15+ anti‐PC antibody synthesis.
The lack of compensatory increases of cells producing anti‐phosphorylcholine antibodies bearing other idiotypes in TEPC‐15 idiotype‐suppressed inbred and outbred mice
Authors: Kim Byung S. , Benewicz Benita J.
Published: February 2007

Idiotype analyses of plaque‐forming cells using anti‐idiotype antibody against TEPC‐ 15 myeloma protein (anti‐T 15 id) indicated that the proportion of plaque‐forming cells producing anti‐phosphorylcholine (PC) antibodies with idiotypic determinants of T15id varied depending on the strain of mice (15–97%). However, treatment of neonates of those mouse strains with the anti‐T 15 id antibody rendered them unresponsive to subsequent stimulation with PC‐containing antigen (<7% of control response). The treatment of spleen cell cultures, derived from adult mice, with anti‐ T15 id antibody resulted in complete suppression of T15 id, although the suppression of the total anti‐PC response was much less pronounced as compared to that induced in vivo. These results suggest that anti‐T 15 id antibodies injected in the neonatal period may chronically inhibit the differentiation of B lymphocytes specific for PC. The lack of compensatory increases in the production of anti‐PC antibodies bearing other idiotypes in T15 id‐suppressed mice does not appear to be related to the clonal proportion of cells producing anti‐PC with non‐T 15 id. This tolerance induction by anti‐idiotype antibody appears to be unique to the nature of clonal differentiation of anti‐PC‐producing lymphocytes.
Antigen‐induced helper and suppressor T cells in normal and agammaglobulinemic chickens
Authors: Chi David S. , Grebenau Mark D. , Thorbecke G. Jeanette
Published: February 2007

Spleen cells from chickens injected with sheep erythrocytes (SE) intravenously 2 to 14 days prior to culture were found to give faster and higher plaque‐forming cell responses upon addition of antigen on day 2 rather than on day 0 of culture. Cell mixture experiments showed that this was due to the induction of suppressor T cells upon re‐exposure to SE on day 0 of culture. Spleen cells taken on days 2 or 14, but not between days 4 and 7 after priming to SE were sensitive to suppression. The suppressor cells were resistant to gamma irradiation (1000 rd) and to mitomycin C, but were apparently lost after 2 days of culture in the absence of antigen. Pokeweed mitogen addition on day 0 of culture also induced suppressor cells, both in SE immune and in normal spleen. Similar suppressor cells were induced in cultures of primed spleen cells taken from agammaglobulinemic chickens. The response to Brucella abortus in vitro was not affected by induction of suppression for the anti‐SE response. Suppression could also be shown after transfer of cell mixtures to irradiated recipients. Helper cell activity for the anti‐SE response could readily be shown, both in vivo and in vitro, in primed spleen cells precultured for 2 days in the absence of antigen, and was also resistant to 1000 rd gamma irradiation and to mitomycin C.
H9/25 monoclonal antibody recognizes a new allospecificity of mouse lymphocyte subpopulations: Strain and tissue distribution
Authors: Takei Fumio , Galfré Giovanni , Alderson Thomas , Lennox Edwin S. , Milstein Cesar
Published: February 2007

C3H/He‐mg mice were immunized with C57 BL/10 (B10) spleen cells and the immune spleen cells were fused with BALB/c myeloma cells (NS1). One of the monoclonal antibodies (H9/25 antibody) produced by the hybrid cells was studied. It reacts with subpopulations of B 10 lymphocytes as well as some lymphoid tumor lines including some of the Abelson virus‐induced leukemias. The antigen recognized by H 9/25 antibody is expressed on lymphocytes from all the B 10 congeneic mice tested as well as some other strains of mice. No linkage between genes coding for the antigen and H‐2 loci was found as judged by its presence on cells of the B 10 strains regardless of H‐2 type and the distribution of the antigen on Bailey recombinant inbred mice. The antigen is expressed on subpopulations of lymph node cells, spleen cells, thymocytes and bone marrow cells. The strain distribution of the H9/25 antigen seems to be identical to that of Ly‐6, Ly‐8 and Ala‐1 antigens. However, the tissue distribution of the antigen recognized by H9/25 antibody, while similar to these alloantigens, is unique and the antigen may be distinct from the other alloantigens.
Natural killer and killer cell activities in patients with primary immunodeficiencies or defects in immune interferon production
Authors: Lipinski Marc , Virelizier Jean‐Louis , Tursz Thomas , Griscelli Claude
Published: February 2007

Natural cell‐mediated cytotoxicity (NCMC) against K‐562 target cells was explored in patients with various primary immunodeficiencies. (a) NCMC was present in 2 patients lacking detectable B cells. Conversely, NCMC was depressed in 2 patients with severe combined immunodeficiency presenting a normal number of circulating B cells. These data exclude a major role for B cells in NCMC. (b) NCMC was depressed mainly in patients with severe combined immunodeficiency or with defects affecting cellular immunity, which suggests a major role in NCMC for cells of T lineage. (c) Four patients with various clinical features associated with a lack of immune interferon production exhibited a strikingly depressed NCMC. Interferon thus appears as a major in vivo activator of natural killer (NK) cell activity. (d) Eight patients exhibiting a depressed NK cell activity had a normal killer (K) cell activity against L1210 cells in the presence of rabbit anti‐L1210 antiserum. These data are consistent with the assumption that NK and K cell activity are mediated through two distinct cellular mechanisms.
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

The 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

Subunit 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.