bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and function of cytotoxic T lymphocytes (CTL). I. In vivo maturation of CTL precursors in the absence of detectable proliferation results as a normal consequence of alloimmunization.
Authors: Kimura A K , Wigzell H 
Published: December 2022

Abstract
In the experiments reported here, we examine the need for cell division as a critical component in the clonal expansion of alloreactive CTL precursors. Unlike previous attempts to inhibit DNA synthesis and cell division non-specifically, we have chosen to follow the normal unimpeded development of CTL in two of the most commonly used in vivo and in vitro allograft systems. The development and relative contribution of CTL lymphoblast-associated cytotoxicity has been followed by density gradient separation and functional analysis of the various fractions of lymphocytes obtained throughout the entire course of sensitization. In addition to the physical parameters (size and density), even more convincing data have been obtained from in vivo administration of 3H-TdR during the entire allograft reaction. The results presented here clearly confirm CTL precursor proliferation in vitro but provide strong evidence that in vivo CTL normally arise via a mechanism independent of blast formation and cellular proliferation. Interpretations of these findings in relationship to the concept of "clonal expansion" for the generation of mature CTL are discussed.
Effects of C-reactive protein on human lymphocyte responsiveness.
Authors: Vetter M L , Gewurz H , Hansen B , James K , Baum L L 
Published: December 2022

Abstract
C-reactive protein (CRP), a trace serum protein that increases markedly in concentration during inflammatory reactions, was recently shown to bind to a subset of human IgG-FcR-bearing peripheral blood lymphocytes in the presence of a ligand such as pneumococcal C-polysaccharide (CPS). CRP has also been detected on a small percentage of PBL that are associated with NK activity. In the present study, we assessed the effects of CRP and CRP-CPS complexes on a variety of human lymphocyte functions in vitro. CRP and CRP complexes significantly enhanced (generally two to threefold) cell-mediated cytotoxicity, minimally enhanced the MLC reaction, and induced a small but regularly detectable blastogenic response in resting PBL. CRP or CRP-CPS complexes had no effect on mitogen-induced blastogenesis, PWM-induced generation of IgM plaque-forming cells, E-rosette formation, antibody-dependent cell-mediated cytotoxicity, or NK activity. The basis for the preferential ability of CRP to enhance cytotoxicity responses in vitro is under further investigation.
Analytical and functional studies on the T cells of untreated and immunologically tolerant diabetes-prone BB rats.
Authors: Naji A , Silvers W K , Kimura H , Bellgrau D , Markmann J F , Barker C F 
Published: December 2022

Abstract
Lymphocyte profiles of untreated diabetes-prone BB rats (BBDP) and their normal marrow-inoculated tolerant littermates were determined with the aid of a fluorescence-activated cell sorter by using monoclonal antibodies specific for rat T cell (W3/13) and T cell subsets (W3/25, T helper; OX8, T cytotoxic/suppressor). In contrast to non-diabetes-prone rats and to their marrow-inoculated littermates, untreated BBDP rats were found to be T lymphocytopenic with reduced W3/25+ cells and with a major loss of OX8+ cells. Moreover, their lymphocytes displayed depressed alloreactivity that was not restored by addition of exogenous IL 2.
IA mutant functional antigen-presenting cell lines.
Authors: Glimcher L H , Hamano T , Asofsky R , Sachs D H , Pierres M , Samelson L E , Sharrow S O , Paul W E 
Published: December 2022

Abstract
We describe a protocol for the selection of mutant cells with an altered pattern of Ia antigenic determinants and antigen-presenting properties from a homogeneous population of functional antigen-presenting cells (APC). The APC line used in this work was obtained by fusing lipopolysaccharide-stimulated B cells from (BALB/c x A/J)F1 donors with cells from the M12.4.1 BALB/c B lymphoma cell line. The resulting hybridomas, including TA3, retained the potent antigen-presenting activity of the parental B lymphoma line and expressed Ia antigens and immune response gene-determined antigen-presenting properties of the A/J type. Mutants of TA3 were obtained by subjecting the cells to negative immunoselection with one monoclonal anti-(alpha) 1-Ak antibody and complement followed by positive immunoselection via electronic cell sorting with a second monoclonal alpha I-Ak or alpha I-Ek antibody. Two types of mutants were obtained. One, A8, appeared to have undergone a fairly limited alteration, since it lost only some of the I-Ak antigenic determinants; the second type appeared to have lost the entire I-Ak molecule but to have retained the I-E molecule. Functional studies with the A8 mutant demonstrated that the loss of a limited number of I-Ak determinants correlated with the loss of a specific I-Ak-encoded restriction element, since A8 failed to present a specific antigen, hen egg lysozyme (HEL), to a HEL-specific I-Ak-restricted T cell hybridoma but retained some capacity to present a second antigen, poly(Glu60Ala30Tyr10) (GAT), to a GAT-specific I-Ak-restricted T cell hybridoma. These results indicate that Ia antigens are the products of immune response gene loci. The availability of such mutants should allow an examination of the relationship between the structure of an Ia molecule and the antigens with which it is co-recognized by T cells.
The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34.
Authors: Gerhard W , Hackett C , Melchers F 
Published: December 2022

Abstract
A T cell line was established in long-term tissue culture from spleen cells of BALB/c mice immunized with influenza virus PR8 (A/PR/8/34(H1N1)) by continuous restimulation with PR8 virus and syngeneic x-irradiated spleen cells. This T cell line and clones derived from it have now been propagated for over 1 yr "in vitro". The T cell line and the clones, upon stimulation with Con A in the absence of antigen and irradiated spleen cells, as upon stimulation in the presence of antigen and adherent cells, produce T cell growth factors, B cell replication and maturation factors, and colony-stimulating factors, as tested by restimulation of proliferation of a clone of cytolytic murine T cells, of lipopolysaccharide-activated B cell blasts, and by macrophage/granulocyte colony formation of murine bone marrow cells, respectively. The T cell line and the clones help syngeneic B cells in the presence of syngeneic irradiated spleen cells and PR8 virus to proliferate and mature into clones of cells secreting virus-specific antibodies. In the presence of PR8 virus and of a bystander antigen, such as sheep red cells, B cells specific for this bystander antigen are also induced. Adoptive transfer of the T cells i.v. into syngeneic nu/nu BALB/c mice enable the recipient mice to produce, upon challenge with PR8, virus-specific antibodies and to clear virus infection of the lung. The virus-specific T cell line and the clones are restricted by H-2 antigens of the d-haplotype, probably by Iad, and recognize a determinant on the hemagglutinin (HA) molecule of PR8 virus. Fifty to 100 fmol of virus-associated or free HA suffice for stimulation as measured by proliferation assays. The stimulating determinant is present on the HA of all natural virus isolates of the H1 subtype, is absent from virus isolates of the H2 and H3 subtypes, and is abolished if glutamic acid at position 115 of the HA1 polypeptide of PR8 is replaced by lysine.
Purification of a major membrane protein of Toxoplasma gondii by immunoabsorption with a monoclonal antibody.
Authors: Kasper L H , Crabb J H , Pfefferkorn E R 
Published: December 2022

Abstract
The principal iodinatable surface protein (P30) of our cloned RH strain of Toxoplasma gondii has an apparent molecular weight of 30,000, as measured by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate under reducing conditions. Monoclonal antibody B specifically immunoprecipitated protein P30 from a detergent extract of surface radioiodinated T. gondii. Monoclonal antibody B in the presence of complement was also parasiticidal for T. gondii, and this parasiticidal effect could be blocked by protein P30. Monoclonal antibody B was purified from mouse ascitic fluid and linked to cyanogen bromide-activated Sepharose. The resulting immunoabsorbent was used to purify 1.7 mg of protein P30 from a large number of parasites. The efficiency of recovery of protein P30 was measured by assays of radioactivity and of parasiticidal blocking activity. Protein P30 represented 3 to 5% of the total protein. It is also present in a recently isolated strain of T. gondii. A convalescent human antitoxoplasma serum immunoprecipitated radiolabeled protein P30. Three convalescent antisera when quantitated by an ELISA test had a high anti-protein P30 titer. Charge shift electrophoresis showed that protein P30 has an extensive hydrophobic region and thus is probably an integral membrane protein. Electrophoresis under nonreducing conditions showed no evidence that protein P30 exists as a disulfide linked homo- or heterodimer, although it probably has intramolecular disulfide bonds.
Analysis of a defect in the H-2 genes of SV40 transformed C3H fibroblasts that do not express H-2Kk.
Authors: Rogers M J , Gooding L R , Margulies D H , Evans G A 
Published: December 2022

Abstract
C3H fibroblasts transformed in vitro with SV40 were adapted to in vivo growth. Several clones were isolated from a single, highly oncogenic tumor and those that displayed oncogenic potential also no longer expressed the H-2Kk molecule. Using the technique of Southern blot hybridization, the H-2 genes and integrated SV40 sequences present in the genomic DNA of several of these clones have been examined and compared with both the parent line and normal liver genomic DNA from C3H mice. All H-2Kk negative clones had altered H-2 genes that appeared as a gain and, depending on the restriction endonuclease, loss of hybridizing fragments compared to normal C3H DNA. A 5.5-kb fragment missing from the Sstl digests of the H-2Kk negative variants was mapped to the H-2Kk region of the major histocompatability complex with the use of congenic mice. This provided direct evidence that a mutation had occurred in the H-2Kk region. The integrated SV40 sequences were similar to those already seen in other SV40 transformed cells and not closely linked to any of the H-2 genes. There was no indication that the H-2 mutation was caused by integration of SV40.
A common VH marker relating BALB/c alpha 1-3 dextran-binding and A/J P-azophenylarsonate-binding antibody families.
Authors: Stanislawski M , Pene J 
Published: December 2022

Abstract
Antibodies that define the idiotypic marker 104E-MPC11 were purified from rabbit anti-M104E sera. The expression of this marker was searched for in a panel of representative myeloma and hybridoma proteins differing in antigen-binding specificities and idiotype expression. By radioimmune competition assays, the marker was distinguished from the IdX Dex idiotype of BALB/c alpha 1-3 dextran-binding proteins (alpha 1-3 Dex-BP) in that it was expressed on both IdX Dex-positive and IdX Dex-negative proteins on the one hand, and on A/J p-azophenylarsonate-binding proteins (Ar-BP) on the other. Among the later, six of eight of the proteins also expressed the major cross-reactive idiotype (CRI). The marker was expressed weakly or not at all on A/J Ar-BP, which did not express the CRI, as well as on a number myeloma and hybridoma proteins of different antigen-binding specificities, and normal IgG. The marker was localized in VH, but its full expression required the light chain, and was influenced by quaternary structure.
Blocking of CTL-mediated killing by monoclonal antibodies to LFA-1 and LYT-2,3. I. Increased susceptibility to blocking after papain treatment of target cells.
Authors: Gromkowski S H , Heagy W , Sanchez-Madrid F , Springer T A , Martz E 
Published: December 2022

Abstract
It is now established that monoclonal antibodies (MAb) against LFA-1 and Lyt-2,3 antigens on cytolytic T lymphocytes (CTL) block killing function in the absence of C. It has been suggested that the blocking is inversely related to CTL-target affinity. In this report, we studied the effect of papain pretreatment of target cells, because papain is known to remove H-2 and to render target cells more resistant to allospecific CTL. CTL-target conjugate formation was weaker with papain-treated target cells (based on reduced post-dispersion lysis in dextran-containing medium). The concentration of MAb required to produce 40 to 60% inhibition of 51Cr release (2-hr assay) was reduced four to 29-fold for alpha LFA-1 and 64 to 114-fold for alpha Lyt-2,3. Papain, however, did not induce blocking by MAb to other CTL antigens such as Thy-1, H-2, and T200. Flow cytometric analysis confirmed that papain selectively removed more than 95% of H-2. In kinetic studies of removal and recovery, H-2 density and conjugate formation correlated well with each other. Sensitivity to blocking was not as well correlated, raising the possibility that an unidentified papain-sensitive target cell molecule other than H-2 plays an important role in CTL-target interaction.
Cell cycle-dependent expression of antigen-binding and I-J-bearing molecules on suppressor T cell hybridomas.
Authors: Takabayashi K , Suzuki N , Kanno M , Imai K , Tokuhisa T , Tomioka H , Taniguchi M 
Published: December 2022

Abstract
The I-J and antigen-binding chains with constant region determinant (Ct) that compose an antigen-specific suppressor T cell factor were found on the surface of suppressor T cell hybridomas, serologically and morphologically demonstrated by a fluorescence-activated cell sorter (FACS) and immunoelectron microscopic analyses. Moreover, the surface expression of the I-J and Ct-bearing chains fluctuating with the same kinetics depended entirely upon the cell cycle. The maximum expression of these two chains was observed in the early stage of the M phase, and the minimum in the S phase. Similarly, the magnitude of the suppressor activity was maximal in the late stage of the M phase, and was minimal in the S phase. The results therefore demonstrated that there exists good correlation between the cell surface expression of the I-J and Ct-bearing chains and the magnitude of the suppressor activity produced. The antigen recognition units on suppressor T cell hybridomas have serologically and morphologically been characterized by using radiolabeled antigens or monoclonal antibodies against the I-J or Ct on the antigen-binding molecule. Cell-binding assay and radioautographic analysis demonstrated that the suppressor T cell hybridoma possesses the capacity to bind native antigen in an antigen-specific fashion as does the hybridoma-derived, antigen-specific suppressor factor composed of the I-J and the Ct-bearing chains, indicating that the recognition unit on the cell surface is composed of a structure similar to the factor.
Immunohistologic and immunoelectron microscopic characterization of the mucosal lymphocytes of human small intestine by the use of monoclonal antibodies.
Authors: Cerf-Bensussan N , Schneeberger E E , Bhan A K 
Published: December 2022

Abstract
Monoclonal antibodies reactive with T cells, T cell subsets, B cells, monocytes, and natural killer cells were used to characterize the nature of mucosal lymphocytes in the human small intestine by application of the immunoperoxidase technique to tissue sections for light and electron microscopic examination. In addition, for comparison, peripheral blood mononuclear cells (PBL) were studied by immunoelectron microscopy. Most of the intraepithelial lymphocytes (IEL) were T cells (Leu-1+, T3+) and expressed the phenotype associated with cytotoxic/suppressor T cells (Leu-2a+, T8+). In contrast, a majority of T lymphocytes in the lamina propria expressed the phenotype associated with helper/inducer T cells (Leu-3a+, T4+). These observations confirm and extend the findings previously reported. In addition, a small number of cells in the lamina propria with the ultrastructural features of macrophages were found to react with anti-Leu-3a and anti-T4 antibodies. Although many IEL contained cytoplasmic granules and had ultrastructural features similar to those of circulating granular lymphocytes, none of these cells reacted with anti-Leu-7 (HNK-1), anti-T10, or anti-M1 antibodies. This suggests that IEL may not be related to circulating large granular lymphocytes, which are Leu-7+, T10+, M1+ and are associated with natural killer activity. Not only Leu-7+ PBL, but T8+, T4+, or T3+ mucosal lymphocytes or PBL also may contain cytoplasmic granules. Therefore, the cytoplasmic granules are not restricted to one cell type, in particular, to Leu-7+ cells.
Immunologic effects of interleukin 2 in primary immunodeficiency diseases.
Authors: Flomenberg N , Welte K , Mertelsmann R , Kernan N , Ciobanu N , Venuta S , Feldman S , Kruger G , Kirkpatrick D , Dupont B , O'Reilly R 
Published: December 2022

Abstract
Five children with primary deficiencies of T cell function were studied to assess the effects of highly purified exogenous Interleukin 2 (IL 2) on their in vitro T cell responses. The lymphocytes from one child with Nezelof's T cell deficiency demonstrated absence of endogenous IL 2 production and improved proliferative responses to mitogen or alloantigen in the presence of exogenous IL 2. Moreover, during in vitro mixed lymphocyte culture in the presence of exogenous IL 2, his lymphocytes were able to develop into cytotoxic effector cells. A second child with Nezelof's syndrome demonstrated a different type of defect. The lymphocytes from this child had less impairment of endogenous IL 2 production. Although IL 2 increased the proliferation of his cells in response to PHA, similar augmentation was not seen after stimulation with OKT3 or alloantigen. In cell-mediated cytotoxicity assays, after mixed lymphocyte culture, natural killer-like activity was strongly boosted in the cultures that contained IL 2, but T cell-mediated cytotoxicity was not. The lymphocytes from three patients with severe combined immunodeficiency did not show improved proliferative responses in the presence of IL 2. Thus, only one of the five patients demonstrated the combination of defective endogenous IL 2 production, but preservation of the ability to respond appropriately to exogenous IL 2. This child may therefore have suffered from a T cell defect pathophysiologically similar to that seen in nude or aged mice.
Attenuation of an adjuvant arthritis by type II collagen.
Authors: Trentham D E , Dynesius-Trentham R A 
Published: December 2022

Abstract
Subcutaneous injection of the nonimmunogenic synthetic alkyldiamine, N,N-diotadecyl-N',N'-bis(2-hydroxyethyl) propanediamine (CP-20961), which possesses potent adjuvant properties for cellular sensitization, can induce an inflammatory arthritis in rats. To study whether a host reaction to native type II collagen plays a role in the pathogenesis of the arthritis in this model, CP-20961-injected Lewis rats received i.v. on four occasions native type II collagen coupled to syngeneic spleen cells with ethylcarbodiimide (CDI), native type II collagen added to spleen cells without CDI, or native type II collagen coupled to rat red blood cells (RBC) with glutaraldehyde. There was a significant suppression of the severity of arthritis in all three groups compared with a control group injected with CP-20961 but not receiving cells. In addition, the prevalence of arthritis was decreased in the group receiving native type II collagen-coupled RBC. Injection of cells coupled to denatured type II collagen, native type I collagen, and ovalbumin did not affect significantly the morphologic aspects of this disease. These data provide evidence that material possessing the quaternary epitope(s) of type II collagen functions in an as yet unidentified effector pathway in this adjuvant arthritis.
Production of a human T lymphocyte chemotactic factor by T cell subpopulations.
Authors: Van Epps D E , Potter J W , Durant D A 
Published: December 2022

Abstract
Concanavalin A-stimulated human peripheral blood mononuclear cells release a lymphocyte chemotactic factor. This lymphocyte chemotactic factor is produced optimally after 24 to 48 hr of culture and is not found before 3 hr of culture, which suggests that the factor is synthesized de novo and is not preformed and secreted after Con A stimulation. This is further supported by experiments showing that the protein synthesis inhibitors cycloheximide and puromycin totally prevent the production of the chemotactic factor. Experiments using cultured and uncultured T lymphocytes as responding cells show that cultured T cells respond more efficiently than uncultured T cells to this factor. Furthermore, the lymphocyte chemotactic factor preferentially stimulates T lymphocyte locomotion as compared to peripheral blood non-T lymphocyte migration. Fractionation of mononuclear cells into glass nonadherent lymphocytes, monocyte-enriched preparations, T lymphocytes, and non-T lymphocytes shows that lymphocyte chemotactic factor is produced by Con A-stimulated, glass nonadherent lymphocytes and T cells but not by monocytes or non-T lymphocytes. Further fractionation of T lymphocytes into Leu-2 and Leu-3 T cell subpopulations shows that the production of T lymphocyte chemotactic factor can be attributed to the Leu-2 suppressor/cytotoxic T cell subset. The generation of a T lymphocyte chemotactic factor by Leu-2 T cells may represent a means of recruiting other T cells to the site of its release.
Generation of low m.w., C3-bearing immunoglobulin in human serum.
Authors: Jacobs R J , Reichlin M 
Published: December 2022

Abstract
The generation of low m.w. C3-bearing immunoglobulin (lg) in normal human serum by an immune complex (IC) model was investigated in vitro by using discontinuous sucrose density gradient centrifugation (DGC) and an assay that measures C3-bearing Ig. In this method developed to measure circulating IC, all C3 and C3-bearing material is precipitated from serum by using anti-C3 sera in C3d antibody excess, and immune precipitated, C3-bearing Ig is quantitated by the uptake of 125I-5S-anti-IgG. When plasma from patients with clinically active systemic lupus erythematosus was assayed after DGC, most of the reactive material was low m.w. (7S), rather than greater than or equal to 19S as expected for IC, in agreement with a previous report. Low m.w., C3-bearing Ig was found in normal EDTA plasma after extended storage at -29 degrees C but not after storage at -70 degrees C. Such material was also generated in normal human serum during incubation at 37 degrees C and its generation was stimulated by the addition of an IC model, high m.w., heat-aggregated IgG (HMW-HAIgG). In experiments in which the participation of serum IgG was monitored by the addition of 125I-7S-IgG and 131I-HMW-HAIgG was used as an IC model, low m.w., C3-bearing Ig was generated exclusively from serum IgG and the amount generated was proportional to the concentration of 131I-HMW-HAIgG. No significant decrease in sedimentation of 131I-HMW-HAIgG was observed, but the ability of anti-C3 sera to precipitate 131I-HMW-HAIgG decreased 66% 4 hr after initial C activation. These results indicate that generation of nascent C3b in serum results in its interaction with monomeric serum IgG, producing low m.w., C3-bearing IgG. In addition, the data indicate that circulating IC that activate C have a brief time span during which they can be detected by methods that depend upon the binding of C3.