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PubMed1975

Properties and activities of transfer factor.

Although there is agreement that transfer factor endows skin test-negative subjects with the ability to develop the delayed allergic responses of the transfer factor donors, there is little direct information on the mechanism of this phenomenon or on the nature of the active components (s). This report reviews some of the known effects of transfer factor or immune responses and inflammation. It is concluded that transfer factor has multiple sites of action, including effects on the thymus, on lymphocyte-monocyte and/or lymphocyte-lymphocyte interactions, as well as direct effects on cells in inflammatory sites. It is also suggested that the "specificity" of transfer factor is determined by the immunologic status of the recipient rather than by informational molecules in the dialysates. Finally, it is proposed that many effects of transfer factor may be due to changes in intracellular cyclic nucleotide content, especially accumulation of cGMP, in immunologically reactive cells.

Antibody Formation↗
PubMed1975

Differences in the surface proteins of mouse B and T cells.

We have selectively labeled the surface of mouse thymus-dependent (T) and thymus-independent (B) lymphocytes by means of lactoperoxidase-catalyzed iodination. Examination of the labeled proteins by electrophoresis in the presence of sodium dodecylsulfate followed by autoradiography revealed differences in the cell surface proteins of B and T cells. Proteins from labeled thymocytes, T cell lymphomas, and both normal and activated peripheral T cells give a broad band of radioactivity corresponding to at least two protein components with apparent molecular weights of 170,000 to 190,000. This band is absent from autoradiographs of iodinated B cell proteins, which instead have another band corresponding to a protein with an apparent molecular weight of about 220,000. We have shown that these T and B cell marker proteins are synthesized by the cell and are not serum components selectively bound to the cell surface. We have also established that these proteins are the major iodinated species precipitated from Nonidet P-40 cell lysates by rabbit anti-mouse lymphocyte serum, suggesting that they are the major antigens recognized by rabbit antibodies to mouse lymphocytes.

Animals↗
PubMed2025

Cancer-testis antigen ACRBP: Cytotoxic response to its HLA-A2 restricted peptide and immune features in ovarian cancer.

While our prior study identified the HLA-A *0201-restricted ACRBP epitope peptide and demonstrated its capacity to generate cytotoxic T lymphocytes (CTLs) in vitro, the clinical relevance of the peptide-induced T cell reactivity in ovarian cancer (OC) patients and the in vivo anti-tumor efficacy of these CTLs remain unexplored. In this study, dendritic cells were sensitized with ACRBP peptide (ALLVLCYSI) and co-cultured with autologous CD8+T cells to induce the production of specific cytotoxic T lymphocytes (Pep-CTLs). The anti-tumor effects of Pep-CTLs were evaluated in SCID mice bearing human ovarian cancer (OC) OVCAR-3 cells. Concurrently, we co-cultured ALLVLCYSI peptide with peripheral blood mononuclear cells (PBMCs) from OC patients (HLA-A2+, ACRBP+) and assessed the number of specific T cells using ELISPOT assays. The immunological impact of the ACRBP peptide against human OC was validated through both in vitro and in vivo experiments. These findings establish a preclinical foundationfor developing ACRBP peptide-based vaccines in OC immunotherapy. To further elucidate ACRBP's role in OC treatment, the study analyzed single-cell RNA sequencing data from 8 OC patients and bulk RNA sequencing data from the Cancer Genome Atlas Project (TCGA) comprising 308 ovarian cancer cases. This analysis aimed to explore the heterogeneity among ACRBP-expressing tumor cell populations and to investigate the correlation between ACRBP expression and immune molecule expression (including MHC and chemokines) alongside chemotherapy response. These insights furnish a theoretical framework supporting the future application of ACRBP in tumor immunotherapy and strategies to prevent immune escape.

Humans↗
PubMed1975

Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras.

Tetraparental bone marrow chimeras were produced by injecting lethally X-irradiated F1 hybrids with relatively high numbers of T-cell-depleted bone marrow cells from both allogeneic parental strains. The mice survival in excellent health and showed a stable, approximately 50:50 (parent:parent), lymphoid cell chimerism lasting for at least 7 mo after irradiation; regeneration of host-type hemopoietic cells was very limited. Thymus, lymph node, and thoracic duct lymphocytes showed specific unresponsiveness to host mixed leukocyte reaction (MLR) determinants. Similarly specific tolerance to H-2 antigens of host type was demonstrated in spleen and lymph node. No suppressor cells could be demonstrated in either system and blocking serum factors could not be found. The results suggest specific deletion of functional T cells reactive to host-type MLR and cell-mediated lympholysis determinants.

Animals↗
PubMed1975

Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.

Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components.

Animals↗
PubMed1975

H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;.

Use of syngeneic, allogeneic, F1, AND H-2 recombinatn mice has shown that animals injected with lymphocytic choriomeningitis (LCM) virus generate T cells which are cytotoxic for H-2K or H-2D compatible, but not H-2 different, virus-infected target cells. Three separate lines of evidence are presented which indicate that these immune T cells are sensitized to "altered-self," the self antigens involved being coded for in the H-2K or H-2d regions. Firstly, cytotoxic activity associated with mutuality at H-2D iy, lysis mediated by immune T cells from F1 or H-2 recombinant mice is specifically inhibited only by presence of unlabeled, virus-infected cells that are H-2 compatible with the targets. Thirdly, LCM-immune F1 and H-2 recombinant T cells inoculated into irradiated, virus-infected recipients proliferate only to kill target cells that are H-2 compatible with both the donor and the recipient. All of these experiments establish that there is a dissociation of T-cell activities between parental haplotypes in F1 mice, and between H-2K and H-2D in recombinants. It would thus seem that there are at least two specificities of tlcm-immune T cells in homozygotes, associated with either H-2K or H-2D, and four specificities in F1 hybrids. The significance of these findings, with respect both to gene duplication and to the marked polymorphism in the H-2 system, is discussed.

Animals↗
PubMed1975

Antibody response in C3H mice injected with CBA lymphoid cells as detected by membrane immunofluorescent staining.

Lymphocytes from CBA mice are strongly responsive to cells from the H-2-identical strain C3H in vitro (MLC), whereas C3H lymphocytes are poorly reactive against CBA cells. Immunization of CBA mice with C3H lymphocytes did not yield any detectable specific antibodies. On the other hand, C3H mice immunized with CBA cells produced specific antibodies as detected by membrane immunofluorescence. Mice of the strains AKR and DBA/2 also possess this specific membrane alloantigen. We thus conclude that it is now possible to discriminate among lymphocytes of CBA and C3H origin.

Animals↗
PubMed1975

Normal and altered phenotypic expression of immunoglobulin genes.

Genetically controlled intraspecific differences between immunoglobulins (allotypes) provide valuable markers for the study of the quantitative expression of allelic and nonallelic alternative forms of immunoglobulins (Igs) during the normal development of rabbits. Heterozygous rabbits are mosaics of cells expressing different Ig-genes since fully differentiated productive cells generally secrete only one of alternative forms of Ig. The proportions of cells that differentiate to produce allelic forms of immunoglobulins during normal development depend on the particular heterozygous genotype. The normal proportions of some markers can be drastically altered if the differentiation of lymphoid cells in the young rabbit occurs in the milieu of antibody specific for one form (allotype suppression). An initiating step in the establishment of persistent allotype suppression is probably the interaction of antiallotype antibody with allotype-bearing receptors on lymphoid cell surfaces, but the mechanism for the maintenance of a state of chronic suppression may well be more complex. Allotype suppression can be viewed as one example of numerous immunological phenomena that reflect specific and finely tuned regulatory mechanisms governing the differentiation and clonal expansion of lymphoid cells destined to secrete immunoglobulins.

Alleles↗
PubMed1975

Identification of lymphoid cells in cultured of murine leukocytes and thymus.

Several culture conditions and media were studied in an effort to establish long-term cultures of murine lymphoid cells from blood and thymus. Cultures vessels included small glass bottles and rubber-stoppered tubes. Media such as Roswell Park Memorial Institute 1640, 1700, 1701, 1715, GEM 1717, NCTC, fetal calf and horse serum supplements, and conditioned medium were tried. Lymphoid cells in mouse leukocyte cultures survived as long as eight months before dying out. However, lymphoid cells in thymus cell cultures, strarted and maintained with GEM 1717 medium with 20% fetal calf serum supplementation, gave rise to cell lines that continued to yield subcultures for more than 2 years. Mcroscopic examination of thymus cell subcultures revealed lymphoid and thymic epighelioid cells. Tumorigenicity studies of one cell line were negative. Chromosomal preparations of this cell line often contained near-normal karyotypes but were complicated by the presence of binucleated cells. Live cell fluorescent antibody assays for surface theta-antigen and immunoglobulin revealed immunoglobulin-negative cells possessing barely detectable theta determinants. Functional assays for thymus-derived lymphoid cell activity suggested that these cells were mitogen responsive and weakly reactive in one-way mixed lymphocyte culture. On the basis of this evidence it was sugguested that these cells represent a class of T-cells (thymus-derived lymphocytes) that have all but lost theta antigen, possibly due to prolonged culture.

Animals↗
PubMed1975

Immunofluorescent studies on antibodies directed to a buried membrane structure present in lymphocytes and erythrocytes.

Brief digestion of human peripheral blood lymphocytes by vibrio cholera neuraminidase (VCN) revealed hidden components of the membrane. Autologous human serums contained antibodies directed to these components that were readily demonstrated by immunofluorescence. Antibodies of similar specificity were found in all normal serums. The antibodies were principally of the IgM variety with lesser amounts of the IgG class present. They were equally active at 4 degrees C and 37 degrees C. The VCN revealed membrane determinants were present in normal B and T lymphocytes, monocytes, lymphocytes of patients with chronic lymphatic leukemia and cells of lymphoid lines. The newly revealed determinants slowly disappeared upon culture of the lymphocytes. These hidden components were similarly demonstrated in erythrocyte membranes and represent the T antigen long known for the red blood cells. Absorption by either VCN treated autologous lymphocytes or erythroyctes removed all of the antibodies capable of reacting with both cell types. Absorption by VCN digested isologous lymphocytes removed all reactivity with autologous lymphocytes.

Absorption↗
PubMed1975

Detection of membrane-associated antigens on lymphoid cells by antibody coupled to staphylococcal protein A.

A simple technique is described for the detection of membrane-associated antigens on lymphoid cells. It is based on the observation that the protein A component of staphylococci binds to the Fc pieces of IgG molecules. Lymphocytes from various sources (mouse, rat, and human tissues) were incubated with hyperimmune antisera directed against surface determinants. Subsequent treatment with a suspension of staphylococci containing protein A permitted visualization of both the presence and distribution of determinants on the cell membrane. The method had comparable sensitivity to the fluorescent sandwich technique and could be used to detect a variety of membrane antigens on both T cells and B cells.

Animals↗
PubMed1975

Cellular basis of the immune response.

Lymphocytes, the cells competent to initiate immune responses, can be divided into two major groups: thymus-derived or T cells responsible for "cellular immunity" (e.g. delayed hypersensitivity reactions) and bursa (or bursa-equivalent) derived or B cells which produce immunoglobulin (antibody) molecules and are involved in "humoral immunity". "Accessory" cells, such as monocytes (or macrophages), polymorphonuclear leucocytes and mast cells act in an auxiliary manner by facilitating antigen processing or presentation, or by liberating factors which modify the various manifestations of the immune response. A variety of interactions between T and B cells and between lymphocytes and accessory cells have been described in both cellular and humoral immunity. Antigen-activated T cells produce factors with various activities: some are involved in recruiting inflammatory cells, others activate macrophages and enhance their microbicidal activities, and others modify B-cell responsiveness either by facilitating or suppressing it. These factors are instrumental in T-cell regulation of immune responsiveness. Antibody produced by B cells also plays a role in immuno-regulation, acting either as an immunopotentiating influence or as a negative feedback, e.g. when complexed with antigen, turning off the response of T or B cells. A detailed knowledge of the precise manner in which cells involved in immunity are regulated is essential for an understanding of how the foetus, an essentially "foreign transplant", can survive to term in its immunologically mature "alien" host.

Animals↗