bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic T lymphocyte responses against alloantigens exhibit preferential effector cell activity for H-2K or H-2D region products similar to that for H-2 restricted responses.
Authors: Lucas C J , Levy R B , Shearer G M
Published: December 2022

The present study was designed to investigate the patterns of allogeneic cytotoxic T cell responses against H-2K and H-2D region products. B10.D2 anti-B10.A(2R) effector cells lysed K-end matched target cells approximately 5 times more efficiently than D-end matched target cells. In contrast, C57BL/10 anti-B10.A effector cells killed K-end or D-end matched target cells equally well, whereas C57BL/10 anti-B10.D2 CTL exhibited a slight preference for D-end matched target cells. These results demonstrate that whole H-2 disparate stimulating populations do not necessarily induce equivalent h-2K and H-2D region-specific CTL responses. The strength of the cytotoxic responses was found to correlate with the number of known serologically detectable specificities shared between the stimulating and target cell populations. The similarities between these allogeneic and MHC-restricted CTL response patterns (which are under Ir-like control) raise the possibility that this regulation reflects the number of K or D region self-antigens that can be recognized in association with a foreign antigenic determinant and suggests that allogeneic responses to major histocompatibility antigens are also self-restricted by MHC gene products. The possibility is considered that such Ir-like control is also a reflection of the amounts of H-2K and H-2D products shed from the cell surface.
An intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of BALB/c mice.
Authors: Brown A R , Nisonoff A
Published: December 2022

This paper describes an intrastrain cross-reactive idiotype, associated with the anti-Ar antibodies of all BALB/c mice tested. The idiotype is present on 20 to 65% of the anti-Ar antibodies of individual BALB/c mice and is localized to the Fab fragment. Adsorption of anti-Ar antibody from an immune serum completely removes the idiotypic activity. Inheritance of the idiotype is linked to the Igh locus, as shown by results obtained with congenic mice. It is present in strains that are Igh-Ia but not in the allotypically related Igh-Ij strains. The idiotype is also present in certain strains belonging to other allotype linkage groups. Expression of the idiotype is suppressed by the administration of rabbit antiidiotypic antibodies before immunization. The BALB/c idiotype is cross-reactive with an idiotype present in a small proportion of anti-Ar antibodies of A/J mice.
Mechanism of T cell activation. II. Antigen- and lectin-dependent acquisition of responsiveness to TCGF is a nonmitogenic, active response of resting T cells.
Authors: Larsson E L
Published: December 2022

Small resting T cells, which do not respond to T cell growth factor (TCGF), acquire responsiveness upon a short (4-hr) pulse of specific ligands by presenting growth receptors for TCGF. The results demonstrate that the same mechanisms operate in the specific induction of primary MLR in that a 5-hr MLR is sufficient to render the responder cells reactive to TCGF. Furthermore, the results demonstrate that an active "response" by the resting T cells is required for expression of functional growth receptors, as demonstrated by the fact that: 1) a 4-hr pulse of concanavalin A (Con A) at 4 degrees C did not result in gain of reactivity to TCGF, whereas a 4-hr pulse at 37 degrees C did; 2) this metabolic requirement for acquisition of responsiveness to TCGF was not due to a secondary requirement for cap-formation of Con A-binding membrane structures, as normal responses were observed in the presence of cytochalasin B (cyt B); 3) the process of Con A-induced acquisition of susceptibility to TCGF was puromycin sensitive.
The role of monocytes in pokeweed mitogen-stimulated human B cell activation: separate requirements for intact monocytes and a soluble monocyte factor.
Authors: Rosenberg S A , Lipsky P E
Published: December 2022

Mononuclear phagocytes (M phi) play an essential role in mitogen-induced proliferation and generation of immunoglobulin-secreting cells (ISC) from human peripheral blood lymphocytes. The nature of this accessory function was examined using the pokeweed mitogen (PWM) model of lymphocyte activation. M phi-depleted human peripheral blood lymphocytes are unresponsive to PWM. Fresh, intact M phi, but not heat-killed M phi, reconstitute the capacity of these cells both to proliferate and generate ISC in response to PWM. In the presence of intact M phi, soluble M phi factors augment PWM-induced generation of ISC but do not enhance 3H-thymidine incorporation. In the absence of intact M phi, the M phi supernatants are unable to support either response. Secretion of active M phi supernatants was completed within the first 24 to 48 hr of incubation, with little additional factor secreted thereafter. Aged M phi, which no longer secreted active factors, fully reconstituted the proliferative response of M phi-depleted lymphocytes; however, they were unable to support PWM-triggered differentiation of B cells into ISC. The addition of active M phi supernatants to the aged M phi restored their capacity to support PWM-triggered generation of ISC. Highly purified Interleukin 1 was also able to enhance the accessory cell function of both fresh and aged M phi in a similar manner. These results suggest that IL-1 is the M phi factor required for the differentiation of human B cells into ISC. Moreover, the data indicate that in the human, M phi accessory cell function involves 2 separate modalities. Both intact M phi and a factor released by fresh M phi (Interleukin 1) are required to support differentiation of B cells into ISC, while only intact M phi are necessary for PWM-induced lymphocyte proliferation.
Autoimmune rat T lymphocytes monospecific for acetylcholine receptors: purification and fine specificity.
Authors: Hohlfeld R , Kalies I , Heinz F , Kalden J R , Wekerle H
Published: December 2022

We prepared highly purified acetylcholine receptor (AChR)-specific T lymphocytes from rats with experimental autoimmune myasthenia gravis (EAMG). Inbred rats were primed with AChR frm 3 different sources: from the electric organs of Electrophorus electricus and Torpedo californica and from denervated rat muscle. After 20 to 30 days, lymphocytes from regional lymph nodes (primary cells) were challenged with soluble AChR in vitro. The activated blast cells were isolated by density gradient centrifugation and allowed to revert back to small secondary lymphocytes in the absence of antigen. These secondary anti-AChR cells were highly responsive to the type of AChR with which they had been primed. Their reactivity critically depended on help by syngeneic accessory cells. Anti-Electrophorus AChR primary and secondary cells cross-reacted detectably with rat AChR and vice versa, whereas anti-Torpedo AChR primary and secondary cells did not significantly cross-react with Electrophorus or rat AChR. Secondary T cells strongly reactive against rat AChR could be selected in vitro from Electrophorus AChR-primed populations by using rat AChR as selecting stimulant. These cells responded equally well against Electrophorus and rat AChR and thus include autoreactive T cell clones.
Detection of shared H-2Kk and H-2Dk antigens that function as self determinants for cell-mediated lympholysis to trinitrophenyl-self.
Authors: Fujiwara H , Levy R B , Shearer G M
Published: December 2022

Spleen cells from C3H/He mice immunized in vivo to trinitrophenyl (TNP)-self were sensitized in vitro to TNP-self. These spleen cells displayed strong lysis on TNP-modified H-2D end-matched (Kd-Dk) targets as well as enhanced cytotoxicity against H-2 matched (Kk-Dk) or H-2K end-matched (Kk-Dd) target cells. Cold target-blocking studies showed that the lysis of TNP-Kd-Dk targets could be blocked by the addition of TNP-modified Kk-Dk, Kk-Dd Kk-Db, or Kd-Dk, but not by TNP-modified Kd-Dd, Kb-Db and Kq-Kq spleen cells. These results demonstrate that the lysis of TNP-Kd-Dk targets is not due to cross-reactive clones against TNP-Kd-Dd, Kb-Db or Kq-Dq antigens. Inhibition of the TNP-Kd-Dk target lysis by TNP-Kk-matched (Kk-Dd or Kk-Db) as well as TNP-Dk-matched (Kd-Dk) blockers also reveals that this target is lysed by clones directed against shared antigens between Kk-TNP and Dk-TNP, indicating that no cytotoxic response restricted for Dk-TNP only could be detected even after in vivo priming.
The fine specificity of immune suppression to individual nucleosides.
Authors: Raps E C , Giroir B P , Borel Y
Published: December 2022

The fine specificity of immune suppression was further studied in a murine experimental model in which the induction and expression of suppression by individual nucleoside-bound spleen cells were examined. The experiments were undertaken: a) to determine whether all 4 nucleosides have the ability to elicit suppressor T cells; b) to examine the specificity of cross-suppression induced by individual nucleosides; and c) to establish that nucleoside-specific suppression is mediated by T cells bearing nucleoside-specific receptors. The results show that, of the 4 nucleosides studied, only guanosine and thymine riboside were capable of eliciting immune suppression. Thymine riboside-coupled spleen cells induced cross-suppression to all 4 nucleosides. Furthermore, the nonresponsive state generated by guanosine-spleen cells was found to be transferable and mediated by nucleoside-binding T cells. The ability of only select nucleosides to elicit immune suppression is discussed in the context of recent evidence demonstrating the selective activation of T cell subsets by intramolecular antigenic determinants.
EAE in rat bone marrow chimeras: analysis of the cellular mechanism of BN resistance.
Authors: Singer D E , Moore M J , Williams R M
Published: December 2022

Unlike Lewis strain, BN rats do not develop EAE when given 10 microgram GPBP + CFA. Their resistance is mediated via the MHC-linked gene Ir-EAE-. The cellular mechanism of BN resistance can be probed using bone marrow chimeras between susceptible LBNF1 strain and BN. F1 leads to BN chimeras can develop EAE when actively sensitized with GPBP + CFA, but are markedly more resistant than F1 leads to F1. By contrast, F1 leads to BN chimeras are highly susceptible to passively transferred EAE from an F1 donor. F1 rats reconstituted with BN bone marrow, i.e., BN leads to F1 chimeras, are completely resistant to EAE induced by active sensitization, but they too are susceptible to passively transferred EAE. We argue that Ir-EAE- blocks the development of T cells reactive to self myelin, and that this occurs at the level of macrophage presentation of antigen to the T cell. Suppressor mechanisms do not appear to play a major role.
Recognition of protozoan parasites by murine T lymphocytes. II. Role of the H-2 gene complex in interactions between antigen-presenting macrophages and Leishmania-immune T lymphocytes.
Authors: Louis J A , Moedder E , MacDonald H R , Engers H D
Published: December 2022

The proliferative response of nylon wool purified, primed lymph node cells to L. tropica parasites in vitro was found to be restored by the addition of either syngeneic or allogeneic adherent spleen cells as a putative source of macrophages. These results suggested a lack of H-2 restriction in Leishmania-specific T cell responses. However, when T cell blasts generated in vitro in response to the parasite were separated on Percoll density gradients and subsequently maintained for 4 days in the presence of TCGF, their response to L. tropica was found to be strictly dependent on the presence of syngeneic spleen cells. Further studies using congenic recombinant mice demonstrated that proliferation of a parasite-specific blasts required the presence of spleen cells compatible with the responding cells in the I-A region of the MHC. This requirement for I-A compatible adherent cells in the spleen cell populations was further confirmed by a lack of proliferative responses in the presence of spleen cells treated with monoclonal anti-la antibodies and complement. Leishmania-immune F1 blasts responding to the parasite in the context of either parental la-bearing accessory cell could be obtained by positive selection from a F1 hybrid responding cell population. Using flow microfluorometry, the T cell phenotype of the L. tropica-specific blasts was determined to be Thy-1+, lyt-1+, and Lyt-2-.
Direct in vitro evidence for different susceptibilities to 4-hydroperoxycyclophosphamide of antigen-primed T cells regulating humoral and cell-mediated immune responses to sheep erythrocytes: a possible explanation for the inverse action of cyclophosphamide on humoral and cell-mediated immune responses.
Authors: Diamantstein T , Klos M , Hahn H , Kaufmann S H
Published: December 2022

Suppressor T cells of humoral immune responses, effector T cells mediating DTH, suppressor T cells of DTH, and helper T cells of humoral immune responses, all with specificity to SRBC, were produced in mice. The biologic activity was tested in adoptive transfer experiments. In vitro treatment with different doses of 4-hydroperoxycyclophosphamide (4-HPCy) yielded the result that the various activities tested were not uniformly sensitive to the action of this drug: Suppressor T cells of humoral immune responses and effector T cells mediating DTH were resistant to doses of 4-HPCy that eliminated the activities of suppressor T cells of DTH and helper cells of the humoral immune response. These findings help to explain the various effects cyclophosphamide has on the in vivo immune response and may help to form a basis for the rational manipulation of the immune response by drugs that selectively affect different subgroups of immune cells.
Developmental changes in humoral suppressor activity released from concanavalin A-stimulated human lymphocytes on B cell differentiation.
Authors: Miyawaki T , Kubo M , Nagaoki T , Moriya N , Yokoi T , Mukai M , Taniguchi N
Published: December 2022

Cell-free culture supernatants (Con A-activated supernatants) were obtained by incubating peripheral blood lymphocytes (PBL) from cord blood, healthy children of various ages, and healthy adults with mitogenic doses of concanavalin A (Con A) for 48 hr. It is well known that human T lymphocytes are activated by Con A to manifest suppressor function in vitro. One mechanism whereby these suppressor cells act has been shown to be by the secretion of a soluble suppressor factor. The present study has investigated the Con A-inducible suppressor cell function in cord blood, children of various ages, and adults by comparing the ability of each Con A-activated supernatant to inhibit the generation of immunoglobulin-producing cells (Ig-PC) in pokeweed mitogen- (PWM) stimulated cultures of adult PBL. Con A-activated supernatants from adults could markedly suppress the generation of Ig-PC by allogeneic as well as autologous PBL in response to PWM. Such suppression appeared to be equally effective on the generation of IG-PC of 3 major classes, IgG, IgM, and IgA. On the contrary, Con A-activated supernatants from cord blood and newborn infants showed only a negligible suppression on PWM-induced adult B cell differentiation. But the suppressor activity found in Con A-activated supernatants gradually increased with advancing age, and reached approximately to the adult level at 4 yr of age or later. The results suggest that human T lymphocytes may be relatively deficient in their Con A-induced suppressor cell function in the early period of life.
Inhibition of complement-mediated functions of human neutrophils by impermeant stilbene disulfonic acids.
Authors: Tauber A I , Goetzl E J
Published: December 2022

The impermeant labeling reagents 4,4'-diisothiocyanostilbene-2-2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid (SITS) inhibited in a concentration-related manner the enhanced generation of superoxide radicals (O2) by human neutrophils engaged in the phagocytosis of zymosan that had been opsonized in fresh serum, without altering the O2 generation by neutrophils exposed to zymosan opsonized in heat-decomplemented serum or to phorbol myristate acetate (PMA). That the stimulus specificity of the suppression of O2 generation by SITS and DIDS is predominantly attributable to an action on neutrophil plasma membrane receptors for complement was suggested by the similarity of the concentration dependence of the inhibition of the expression of neutrophil C3b receptors, as assessed by a rosetting assay. Washing neutrophils that had been pretreated with the covalent label DIDS failed to reverse either the suppression of C3b-dependent rosetting or the inhibition of O2 generation stimulated by opsonized zymosan. In contrast, pretreatment with DIDS and washing or erythrocytes bearing C3b and of opsonized zymosan did not inhibit their capacity to form rosettes and to stimulate O2 generation by neutrophils, respectively. In the same rosetting assay, the expression of IgG-Fc receptors was unaffected by SITS and DIDS. The rapid and apparently selective inhibition of the expression of neutrophil C3b receptors by noncytotoxic concentrations of the impermeant stilbene disulfonic acids may provide a means to analyze the complement dependence of other neutrophil effector functions.
Human B lymphocytes activated by Epstein-Barr virus (EBV) or by mitogens suppress mitogen-induced immunoglobulin production.
Authors: Tsukuda K , Berczi I , Klein G
Published: December 2022

Polyclonal activation of human B lymphocytes by LPS or protein A, alone or in combination or by Epstein-Barr virus (EBV), generates suppressive conditions that inhibit the response of human B lymphocytes to pokeweed mitogen (PWM), measured by the induction of immunoglobulin-secreting cells (PFC). Moreover, EBV-transformed B cell lines of normal or neoplastic (Burkitt lymphoma) origin also suppressed the PWM-induced immunoglobulin production of normal B cells. Cell separation experiments have shown that mitogen activated autologous B cells stimulate suppressor T cells in a similar way as B cell-derived lymphoblastoid cell lines. The significance of this phenomenon is considered in relation to the escape of the activating microorganism or virus from immune control and the occurrence of network interactions within the immune system.
Regulation of paralytic experimental allergic encephalomyelitis in rats: susceptibility to active and passive disease reinduction.
Authors: Hinrichs D J , Roberts C M , Waxman F J
Published: December 2022

Spleen cells obtained from Lewis inbred rats previously immunized with 50 microgram of guinea pig basic protein emulsified in complete Freund's adjuvant passively transferred paralytic experimental allergic encephalomyelitis (EAE) only following an in vitro conditioning period. The in vitro conditioning required the presence of either concanavalin A or encephalitogenic antigen. The conditioned cells caused passive paralytic EAE in recipients of 10 million viable cells. After recovery from passive paralytic EAE, animals were completely susceptible to additional attempts to induce EAE by active or passive means. Active EAE recovered rats were resistant to additional attempts to induce active EAE but were fully susceptible to passively induced EAE mediated by in vitro conditioned cells.
Immunosuppressive effect of mouse serum lipoproteins. I. In vitro studies.
Authors: Hsu K H , Ghanta V K , Hiramoto R N
Published: December 2022

Three classes of lipoproteins, very low, low, and high density, were isolated from normal mouse sera and characterized with respect to electrophoretic mobility, content, and composition. All 3 classes of mouse serum lipoproteins migrated into the alpha region at different rates and were composed of more phospholipid and less triglyceride and cholesterol than lipoproteins from man. High density lipoprotein (HDL) was the major lipoprotein, carrying 70% of the serum cholesterol and phospholipid and 85% of the total lipoprotein. Whole mouse serum and all classes of mouse serum lipoproteins inhibited lymphocyte proliferation stimulated by mitogens. No strain specificity was observed. HDL contributed about 73% of the total inhibitory activity. The effect of apoprotein and the lipid portion of very low, low, and high density lipoproteins were also studied.
Alkaline phosphatase in hematopoietic tumor cell lines of the mouse: high activity in cells of the B lymphoid lineage.
Authors: Culvenor J G , Harris A W , Mandel T E , Whitelaw A , Ferber E
Published: December 2022

Alkaline phosphatase (EC 3.1.3.1) was assayed in a large number of cultured mouse tumor cell line using p-nitrophenylphosphate as the substrate. Of 19 lines of the B lymphoid lineage, including Abelson pre-B, B lymphoma, and plasma cell tumor lines, all but 1 had substantial activity averaging 407 nmol/min/mg protein (with a range from 5 to 900). Nine T lymphoid and 9 nonlymphoid hematopoietic lines examined had low activity of 0.7 to 4.2 nmol/min/mg protein. The enzyme was markedly enriched in plasma membrane preparations from the B lymphoid cells, but not in those from most T lymphoma cells. The activity of another plasma-membrane-bound enzyme, gamma-glutamyl transferase, did not vary systematically with the type of cell line but was exceptionally high in 1 T lymphoma line. Investigation of pH dependence and susceptibility to inhibition by L-phenylalanine and L-homoarginine indicated similarity of the alkaline phosphatase from B cell lines to the enzyme recoverable from normal mouse kidney, placenta, bone marrow, and lymphoid organs. The enzyme seems to provide a useful marker for tumor lines of the B lymphoid lineage and for their plasma membranes.
Studies on natural killer (NK) cells. I. NK cell specific antibodies in CE anti-CBA serum.
Authors: Burton R C , Winn H J
Published: December 2022

An antiserum prepared by injecting CE mice with CBA spleen cells has been shown to contain antibodies specifically reactive with NK cells. The serum also contains antibodies detectable in C-dependent dye exclusion tests, but in a study of (CE X CBA)F1 X CE mice reactivity in this test was found to segregate independently of sensitivity of NK cells to inactivation. Moreover, abrogation of NK activity was observed with concentrations of antiserum and C that were considerably lower than those required for detectable cytotoxicity as measured by dye uptake. Thus, it is possible to use this antiserum for the selective removal of NK activity. Analysis of the strain distribution of NK cell sensitivity to CE anti-CBA serum suggests that this reagent may detect an allele of the NK-1 system, and we have tentatively designated the allelic product as NK-1.2, and the corresponding antibodies as anti-NK-1.2. However, the possibility that CE anti-CBA serum detects a new system of NK-specific antigen has not been excluded.
Cell-mediated immunity in interstitial nephritis. IV. Anti-tubular basement membrane antibodies can function in antibody-dependent cellular cytotoxicity reactions: observations on a nephritogenic effector mechanism acting as an informational bridge between the humoral and cellular immune response.
Authors: Nielson E G , Phillips S M
Published: December 2022

Anti-tubular basement membrane antibodies (alpha TBMA) were tested in vitro in an antibody-dependent cellular cytotoxicity (ADCC) reaction utilizing tubular antigen-coated targets. A selected subpopulation of normal guinea pig spleen cells induced significantly more target cell lysis in the presence of sera containing alpha TBMA than in the presence of control sera. this ADCC reaction using alpha TBMA exhibited a characteristic dose responsiveness and the alpha TBMA binding was specific for species-independent tubular antigens. The spleen effector cells used in this assay were characterized as nonadherent, non-T cells bearing Fc-receptors similar to other previously described natural killer cells found in guinea pigs. These studies suggest that natural surveillance systems may be able to use alpha TBMA as an informational bridge to tubular antigens. Such a potential nephritogenic effector mechanism has not been previously described.
Tumor cell destruction by cytotoxic T lymphocytes: the basis of reduced antitumor cell activity in syngeneic hosts.
Authors: Fishelson Z , Berke G
Published: December 2022

Tumor overgrowth in spite of an ongoing antitumor immune response may be due to a basic immunologic defect in T cell-mediated responses against the potentially immunogenic tumor cells. To further understand T cell-mediated responses in syngeneic tumor-host systems, we have analyzed the interaction of cytotoxic T lymphocytes (CTL) with syngeneic tumor cells and have compared it with CTL-allogeneic tumor cell interaction. The major conclusions of this study are: 1) Syngeneic and allogeneic CTL lyse target cells through a similar mechanism. 2) The reduced reactivity in the syngeneic system is due to the low content of effector cells capable of binding to and killing tumor cells. 3) The avidity of CTL-syngeneic tumor cell binding is lower than CTL-allogeneic tumor cell binding. We suggest that the latter 2 observations result from a low immunogenicity of tumor cells in the syngeneic host.
Simultaneous induction of antigen-specific IgA helper T cells and IgG suppressor T cells in the murine Peyer's patch after protein feeding.
Authors: Richman L K , Graeff A S , Yarchoan R , Strober W
Published: December 2022

The effects of feeding the dietary protein antigen, ovalbumin (OVA), on OVA-specific IgG and IgA immune responses involving Peyer's patches (PP) and mesenteric lymph nodes (MLN) were examined. Mice were administered soluble OVA by gastric intubation. One to 3 days later, PP, MLN, or spleen cells from these donor mice were adoptively transferred into normal syngeneic recipients. After two subsequent immunizations, spleens from the recipient mice were assayed for IgA and IgG anti-OVA plaque-forming cell (PFC) responses. None of the tissues from normal (unfed) mice had the inherent ability to alter recipients' IgG or IgA PFC responses. Within 1 day of OVA feeding, however, cells were generated in the PP that could augment recipients' IgA anti-OVA PFC responses and suppress IgG PFC responses. Three days after OVA feeding, these cells were present in MLN as well, and whereas the IgG suppressor cell also appeared to migrate to spleen, the IgA helper cell did not. The cells mediating antigen-specific IgG suppression and IgA help were both T cells but could be distinguished by surface phenotype. We therefore conclude that protein feeding induces differential, isotype-specific immunoregulation in gut-associated lymphoid tissues, part of which is mediated by an antigen-specific IgA helper T cell.
Interaction between Entamoeba histolytica and the immune system. I. Mitogenicity of Entamoeba histolytica extracts for human peripheral T lymphocytes.
Authors: Diamantstein T , Klos M , Gold D , Hahn H
Published: December 2022

The effect of Entamoeba histolytica extracts (E.h.e.) on proliferation in vitro of human peripheral blood lymphocytes, cord blood lymphocytes, and lymphocytes enriched for T cells or non-T cells was investigated. As tested by 3H-thymidine uptake and by morphologic criteria, E.h.e. stimulate T lymphocyte proliferation. Non-T lymphocytes do not respond to E.h.e. The response of lymphocytes to E.h.e. differed from their response to Con A in several respects, indicating either that E.h.e. and Con A act on different subsets of T cells or that E.h.e. act by different mechanism on the Con A reactive cells.
Deficiency of autologous mixed lymphocyte reactions and serum thymic factor level in Down's syndrome.
Authors: Franceschi C , Licastro F , Chiricolo M , Bonetti F , Zannotti M , Fabris N , Mocchegiani E , Fantini M P , Paolucci P , Masi M
Published: December 2022

The immune competence of the T lymphocyte system was studied in 28 noninstitutionalized subjects with Down's syndrome (DS) and were compared with sex- and age-matched healthy controls. The ability of enriched T lymphocytes to respond to 3 different T cell stimulants revealed a selective impairment of T lymphocyte subset(s). Subjects with DS showed normal responsiveness in allogeneic mixed lymphocyte reactions, but their response to phytohemagglutinin and in autologous mixed lymphocyte reactions was severely impaired. Non-T cells from DS subjects stimulated equally well both normal and DS allogeneic T lymphocytes. The blood concentration of serum thymic factor in the majority of DS subjects was much lower than that found in age-matched healthy controls. These data support the hypothesis that a deficiency of the T-dependent regulatory system is an intrinsic feature of DS and confirm the precocious aging of the immune system in these subjects.
Kinetics of cytolytic T lymphocyte binding to target cells in suspension.
Authors: Balk S P , Walker J , Mescher M F
Published: December 2022

Cytolytic T lymphocytes (CTL) were able to specifically bind and lyse allogeneic P815 tumor cells and LPS blast cells in suspension. An assay was developed to measure the rate of target cell binding in suspension independent of the rate of lysis. Target cell binding was found to plateau within 3 hr in suspension. The presence of free, functional CTL and targets at these plateaus was demonstrated, indicating that target cell binding was an equilibrium process. Scatchard plots were used to derive values for Kd (apparent affinity) and bmax (maximum binding). Target cell binding in suspension could not be blocked by purified plasma membranes. Target cell binding was compared for CTL generated by secondary in vitro stimulation with intact cells or with purified membranes. These 2 CTL populations yielded distinct values for Kd and bmax. Implications of this kinetic difference for CTL recognition of purified plasma membranes are discussed.
Serologic and structural characterization of immunoglobulin chains secreted by rabbit-mouse hybridomas.
Authors: Yarmush M L , Gates F T , Dreher K L , Kindt T J
Published: December 2022

Serologic and primary structural analyses of Ig chains secreted by several rabbit-mouse hybridomas have shown that these hybrid cells produce heavy (H) or light (L) chains identical to those isolated from rabbit sera. Two of the cell lines (7D2, 7D6) secreted rabbit H chains with a m.w. of 55,000 each of which expressed a full complement of variable and constant region allotypes (a3, d11, e15). These apparently normal rabbit H chains were secreted in a complex with a m.w. about 130,000, and serologic studies indicated that this complex contained a covalently linked mouse kappa L chain. Two other cell lines (4C1, 12F2) produced allotype b4 L chains with m.w. of 23,000 and 25,000, and a third (1D4P5) produced an allotype b5 L chain with a m.w. of 23,000. Serologic analyses indicated that the allotypes on these chains are equivalent to those expressed by normal rabbit Ig molecules. Partial amino acid sequence data obtained for the L chain products showed them to be typical of rabbit L chains, and to be significantly different from mouse L chains.
Immune complexes in tissues of obese strain (OS) chickens.
Authors: Katz D V , Kite J H , Albini B
Published: December 2022

Obese strain (OS) chickens develop spontaneous autoimmune thyroiditis (SAT) comparable in many aspects to human Hashimoto's thyroiditis. In a chronologic study on chickens of the Obese strain with B1B1 and B4B4 genotypes, immune and electron dense deposits suggesting immune complexes (IC) were found in the basal lamina of thyroid follicles (BLTF) as early as the time of hatching. The incidence of IC deposition in BLTF increased with age. In some of the chickens studied, thyroglobulin could also be demonstrated in the immune deposits. In addition, IC were also detected in the glomerular basement membrane of kidneys and in basement membranes of cecal tonsils. The early occurrence of IC in tissues of OS chickens suggests a possible primary role of these immune reactants in the pathogenesis of SAT.
Seeding of the 10-day mouse embryo thymic rudiment by lymphocyte precursors in vitro.
Authors: Fontaine-Perus J C , Calman F M , Kaplan C , Le Douarin N M
Published: December 2022

The thymic rudiment was removed from the mouse embryo at 10 days of gestation, while it was still included in the 3rd branchial arch. When cultured alone, either in vitro or on the chick chorioallantoic membrane (CAM), it failed to develop as a lymphopoietic organ and remained in an epithelial state. If it was associated in transfilter culture with various types of hemopoietic organs from either embryonic or adult mice (e.g. yolk sac, fetal liver, thymus, bone marrow), it became seeded by lymphoid precursor cells and underwent a normal histogenetic process. If the donor and the receptor explants belonged to different strains of mice, the thymus that developed in culture was chimeric: thymic stroma cells (i.e., epithelial and connective cells) were of the receptor explant type, whereas the lymphoid population was of the donor type. Two genetic markers were used to label the thymic cell types, the Thy-1-1-Thy-1-2 system and the isozymes of the glucose phosphate isomerase.
Adoption of tumor immunity: role of the major histocompatibility complex.
Authors: Poupon M F , Payelle B , Lespinats G
Published: December 2022

T cells from spleens of mice immunized against a chemically induced tumor were able, when transferred to normal syngeneic mice together with tumor cells, to protect adoptively against tumor growth. The inability of such cells to identically protect pangenic nude mice and F1 hybrid mice, and the incompetence of T cells alone in the in vitro tests indicated that the T cells by themselves were unable to kill the tumor cells. We hypothesized that the protection transmitted by spleen T cells results from an interaction with the recipient mouse and that this interaction is controlled by the major histocompatibility complex (MHC). Analysis of the lack of protection at the level of the MHC subregion demonstrated that in the transfer of immune spleen T cells from parent mice to F1 recipient mice, an identity of the KIA subregion permitted a complete transfer of protection. In the transfer of immune spleen T cells from F1 mice to parent recipients, a semi-identity of the KIA subregion was sufficient but a complete identity of the H2D subregion was necessary. The use of such a model, requiring the transfer of parental cells to F1 hybrid mice, necessitated the analysis of the possible role of the hybrid resistance gene. We have demonstrated the absence of correlation between the hybrid resistance and the adoptive protection. At the present stage of this work, the adoptive neutralization test allows us to conclude that the immunologic rejection of a chemically induced tumor is the result of interaction between 2 cells, a T cell and a radioresistant non-T cell.
Preferential reactivity of certain human and rabbit IgM and IgG rheumatoid factors with mildly reduced and amidomethylated IgG.
Authors: Brown C S , Brown J C
Published: December 2022

Two broadly defined populations were identified in affinity column-enriched rabbit and human rheumatoid factor (RF) preparations: one population reacted preferentially with mildly reduced and alkylated (MRA) homologous (with regard to species) IgG, and the other reacted preferentially with native, intact IgG. Each of these reactivities was identified by preferential association of RF with either intact or MRA IgG-Sepharose 4B conjugates and existed in both the IgM and IgG immunoglobulin classes. Use of soluble IgG inhibitor preparations in RF- dependent hemolytic and hemagglutination inhibition in RF-dependent hemolytic and hemagglutination inhibition assays showed that the preferred form of IgG inhibitor paralleled the preference of a particular RF preparation for a particular IgG affinity matrix. In addition, preferential reactivity was observed toward either intact or MRA Fc gamma inhibitors. On a molar basis RF reactivity with Fc gamma was significantly less than that observed in the presence of whole IgG. In contrast, neither IgG Fab nor F(ab')2 fragments were reactive with either of the 2 specificity populations of RF. The distribution of immunoglobulin class relative to specificity suggested that preferential reactivity with MRA IgG was usually associated with IgM RF, and reactivity with intact IgG was usually associated with IgG RF. These data suggest that in vivo perturbation of IgG structure may lead to an RF response identifiable by reactivity with an altered monomeric form of IgG.
Functional subsets of B cells defined by quantitative differences in surface I-A.
Authors: Greenstein J L , Lord E M , Horan P , Kappler J W , Marrack P
Published: December 2022

The quantitative expression of surface I-A determinants has been used to define functional B cell heterogeneity based on responsiveness to the trinitrophenyl (TNP) hapten on various classes of carrier molecules. Unprimed, anti-Thy 1 and complement-treated B10.A (I-Ak) B cells were stained with a monoclonal anti-I-Ak reagent that had been fluorescein (FL) conjugated. By using a fluorescence-activated cell sorter these cells were then sorted into 2 populations of cells staining heavily or lightly with this reagent. These populations of cells were then assayed for anti-TNP precursor frequency, in responses to 3 TNP-antigens, by limiting dilution analysis. B cells responsive to TNP-lipopolysaccharide (LPS) and TNP-sheep red blood cells (SRBC) were found in both the B cells that expressed a low amount of surface I-A and the B cells that expressed a high amount of I-A. However, B cells with the ability to respond to TNP-Ficoll were found only in the B cells that expressed a low amount of surface I-A. These experiments suggest that the quantitative expression of surface I-A can be used to define B cell populations with different abilities to respond to hapten coupled to Ficoll.
Antibody-dependent, cell-mediated cytolysis (ADCC) with antibody-coated effectors: rat and human effectors versus tumor targets.
Authors: Jones J F , Titus J A , Segal D M
Published: December 2022

We have previously described techniques that cause antibody molecules to remain bound to P388D1 cells for at least 18 hr, and enable these cells to lyse hapten-coated erythrocytes not sensitized with antibody. These methods collectively are called "franking." In this study, we have determined that these methods are applicable to other systems. We franked rat splenocytes and human peripheral blood leukocytes with rabbit anti-TNP antibody, and showed that they were capable of lysing TNP-tumor and erythrocyte targets (not coated with antibody) in a hapten-specific, antibody-dependent fashion. Both the mononuclear and the polymorphonuclear (PMN) leukocyte fractions of the human cells were capable of mediating lysis. Additionally, human leukocytes franked with rabbit antibody were stained with fluorescent goat anti-rabbit IgG Fab, and were analyzed for fluorescence by flow microfluorometry. Nearly all of the PMN cells and about one-half of the mononuclear cells had IgG on their surfaces after franking. Clearly, not all cells can be franked, but those that can retain significant numbers of antibody molecules (approximately 5 X 10(4), in the case of PMN cells) on their surfaces.
The protective antigen of malarial sporozoites (Plasmodium berghei) is a differentiation antigen.
Authors: Aikawa M , Yoshida N , Nussenzweig R S , Nussenzweig V
Published: December 2022

Pb44, the protective antigen of rodent malaria sporozoite (Plasmodium berghei) covers the entire surface of mature, salivary gland sporozoites. This antigen is undetectable in approximately 50% of the immature, i.e., oocyst sporozoites. On the surface of the remaining oocyst sporozoites, Pb44 is found in patches. Pb44 is present in early exoerythrocytic liver stages of P. berghei but is present in early exoerythrocytic liver stages of P. berghei but becomes undetectable after 30 hr of intrahepatocytic development. It seems likely that Pb44 is a differentiation antigen associated with an unique function of the sporozoites, perhaps penetration in the target host cells.
Experimental anti-alveolar basement membrane antibody-mediated pneumonitis. I. The role of increased permeability of the alveolar capillary wall induced by oxygen.
Authors: Jennings L , Roholt O A , Pressman D , Blau M , Andres G A , Brentjens J R
Published: December 2022

Attempts to produce in animals lung lesions mediated by anti-alveolar basement membrane (ABM) antibodies have thus far been inconclusive. The aim of the present study was to test the hypothesis that increased permeability of the endothelial cell lining is needed before circulating antibodies can gain access and bind to ABM. A goat antiserum was prepared against purified rabbit ABM. After i.v. injection of the gamma-globulin fraction into rabbits, goat IgG was detected in glomerular basement membrane but not in ABM. However, 17 of 19 rabbits injected with anti-ABM antibody after exposure for 62 to 66 hr to 100% oxygen had a diffuse linear binding of goat IgG in ABM and died with pulmonary edema and hemorrhagic pneumonitis. By the paired label isotope technique, uptake of anti-ABM antibodies in lung far exceeded that in kidney. Semiquantitative histologic studies indicated that the lesions in the lung of these rabbits were more severe then those found in rabbits exposed to 100% oxygen and injected with normal goat serum gamma-globulin. None of the latter animals died with pulmonary edema; none was found to have binding of goat IgG in the lung. The results indicate that under normal physiologic conditions the endothelium is a barrier that prevents binding of IgG antibodies to ABM. The increased permeability induced by oxygen in the alveolar capillary wall is a nonimmunologic factor allowing the development of a reproducible model of severe anti-ABM antibody-mediated pneumonitis.
Glucocorticoid-induced membrane alteration of thymocytes and thymic phagocytosis.
Authors: Miyazawa T , Sato C , Kojima K
Published: December 2022

Electrophoretic mobility (EPM) of thymocytes progressively decreased after an i.p. injection of 10 mg hydrocortisone, and reached its lowest value 3 hr later. The degree of the decrease in the EPM of thymocytes was dependent on the dose of hydrocortisone. Thymic phagocytic cells began to ingest thymocytes in vivo 2 hr after hydrocortisone injection, and thymic phagocytosis continued up to 8 hr. Glucocorticoid-induced phagocytosis was also detected in vitro, i.e., primarily cultured thymic phagocytic cells ingested membrane-altered viable thymocytes from 10-mg hydrocortisone-treated mice 4 to 10 times more than control thymocytes. It was considered from these results that the decrease in the negative surface charge of thymocytes is closely associated with the phagocytosis of thymocytes by thymic phagocytic cells.
F1 hybrid-anti-parental H-2b cell-mediated lympholysis: genetic control of target antigens by the H-2D region.
Authors: Nakano K , Nakamura I , Cudkowicz G
Published: December 2022

The immunogenetic specificity of (C57BL/6 X DBA/2)F1 anti-parental C57BL/6 cytotoxic T lymphocytes (CTL) induced in primary mixed spleen cell cultures was determined in direct lytic and competitive inhibition assays. A large panel of peritoneal exudate cells (PEC) bearing nonrecombinant and recombinant H-2-Tla haplotypes was the source of target and inhibitor cells. All PEC of H-2b, H-2bc, H-2j, and H-2ja types, irrespective of background genetic constitution, were as susceptible to direct lysis as C57BL/6 PEC, but PEC of H-2a, H-2d, H-2k, H-2q, H-2s, and H-2u types were not. The possible involvement of the Tla region in controlling target antigens was excluded by testing PEC obtained from 4 H-2/Tla or intra-Tla recombinant mouse strains. The genes controlling target antigens were mapped to the D region with the aid of 9 intra-H-2 recombinants; for target PEC to be lysed it was necessary and sufficient that Db antigens be part of the H-2 phenotype. These results were confirmed by competitive inhibition assays. Resident peritoneal cells not exposed to fetal bovine serum were also lysed by F1 anti-parental H-2b CTL, a demonstration that target antigens are expressed on normal cells.
Correlation of the biologic responses of C3H/HEJ mice to endotoxin with the chemical and structural properties of the lipopolysaccharides from Pseudomonas aeruginosa and Escherichia coli.
Authors: Pier G B , Markham R B , Eardley D
Published: December 2022

The basis of the biologic responses of C3H/HeJ mice to endotoxin administration in relation to the structural linkages in the lipid A portion of the lipopolysaccharide (LPS) of Pseudomonas aeruginosa and Escherichia coli were investigated. P. aeruginosa LPS was found to be immunogenic, mitogenic, and toxic, but not lethal, in C3H/HeJ mice. The observed mitogenicity in spleen cells was directed toward immunoglobulin- (Ig) bearing cells, was present in response to isolated and solubilized lipid A, and was inhibitable by polymixin B. The P. aeruginosa LPS was chemically analyzed in order to define its composition and exclude the presence of contaminating proteins being responsible for the biologic responses of C3H/HeJ mice that were observed. Structural analysis of the linkages of the fatty acids to the glucosamine backbone in the lipid A of P. aeruginosa and E. coli revealed similarities in terms of the ratio of hydroxy fatty acids to straight chain fatty acids and the way in which these 2 types of fatty acids were linked to the backbone. Differences were seen in the carbon chain length of the fatty acid substituents, and the substituent on the hydroxy fatty acid that is directly ester linked to the glucosamine backbone. These data indicate that the refractivity of C3H/HeJ mice to the biologic effects after the administration of Gram-negative endotoxins may be limited to enterobacterial LPS. Those differences we found in the chain length and/or linkages of the fatty acid substituents in the lipid A portion of the LPS between P. aeruginosa and E. coli may be sufficient to render C3H/HeJ mice responsive to the biologic effects of nonenterobacterial endotoxins.
The role of transmethylation reactions in regulating the binding of BCG-activated murine macrophages to neoplastic target cells.
Authors: Adams D O , Pike M C , Snyderman R
Published: December 2022

The ability of BCG-activated macrophages from C57BL/6J mice to lyse neoplastic targets was depressed by inhibitors of methyltransferase reactions (10(-4) M adenosine, 10(-5) M EHNA, and 10(-4) M L-homocysteine or 10(-5) M DZA). Binding of P815 mastocytoma targets to BCG-activated macrophages, which has been shown to be a necessary event in cytolysis of those targets, was also inhibited by adenosine, EHNA, and L-homocysteine or by DZA at the above concentrations. Inhibition of binding was obtained when macrophages were pretreated with the inhibitors, whereas pretreatment of targets with the inhibitors did not alter binding. The inhibitors were not toxic to the macrophages, as judged by morphology and viability of the macrophage cultures as well as by ability of macrophages to bind antibody-coated P815 targets or to secrete plasminogen activator. The inhibitors, at concentrations that inhibited cytolysis and binding, also depressed one type of S-adenosyl-L-methionine-mediated methylation reaction (protein carboxy-O-methylation) in BCG macrophages. The data suggest that transmethylation reactions are essential for the ability of BCG activated murine macrophages to bind and, hence, to destroy P815 tumor cells.