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J D Levich

Publications and source records attributed to J D Levich.

6 recordsLinked to original sources

Anti-RNA polymerase I antibodies in the urine of patients with systemic lupus erythematosus.

Urine samples from patients with systemic lupus erythematosus (SLE) (n = 80), patients with rheumatoid arthritis (RA) (n = 21), and healthy controls (n = 36) were analyzed by radio-immunoassay (RIA) for anti-RNA polymerase I (RPI) antibodies. Significant levels of anti-RPI antibodies were detected in the urine of 46% of the patients with SLE but in only 19% of the patients with RA and in no sample from healthy individuals. The presence of anti-RPI antibodies in the urine was confirmed by demonstrating that IgG purified from the urine of patients with SLE was capable of inhibiting the transcriptional activity of RPI in vitro. If the quantity of anti-RPI antibodies excreted is related to disease activity, analysis of urine for these antibodies may be a useful alternative for the purpose of monitoring the progression of disease in individuals with SLE because of the ease by which the sample can be collected.

Adolescent↗

Macrophage handling of a tolerogen and the role of IL 1 in tolerance induction in a helper T cell clone in vitro.

The human gamma-globulin (HGG)-specific helper T cell clone AB.7.D7 can reconstitute the plaque-forming cell response of HGG-primed B cells. Tolerance induction at the level of T cell help results from exposure of the AB.7.D7 cells to 10 micrograms monomeric HGG. The monokine IL 1 was found to interfere with tolerance induction in AB.7.D7 cells in a dose-dependent manner. Furthermore, interference with tolerance induction was dependent upon the T cells being presented with IL 1 at the same time as monomeric HGG, the tolerogen. IL 1 and monomeric HGG could not be demonstrated to interact to make nontolerogenic soluble aggregates, however. It was found that monomeric HGG was unable to stimulate the production of either membrane or secreted IL 1 by splenic macrophages and in addition was not degraded by peritoneal exudate cells. Heat-aggregated HGG, which is highly antigenic and nontolerogenic, is a good stimulus for IL 1 production and is processed by macrophages into peptides of varying sizes. These data are consistent with the suggestion that a tolerogenic signal results from T cell recognition of a nondegraded antigen in the absence of a signal from IL 1. It is possible, however, that small amounts of processed antigen, undetectable by us, are involved.

Animals↗

Tolerance induction in antigen-specific helper T cell clones and lines in vitro.

The induction of T cell tolerance in vitro was investigated by using HGG-specific murine helper T cell (Th) clones and cell lines. It was found that exposure of Th to monomeric HGG (tolerogen) for 18 hr rendered the Th unable to reconstitute the PFC response of HGG-primed B cells. The tolerant state was not a result of Th cell death, as up to 100% of Th could be recovered after exposure to the monomer, and in addition, the recovered cells proliferated in response to IL2. B cells were shown not to be significantly affected by the presence of monomeric HGG in amounts calculated to be carried over from the tolerization cultures into the assay cultures. Consequently, it was concluded that interaction between Th and monomeric HGG induced unresponsiveness at the T cell level. A comparison of the tolerogenic potential of monomeric, soluble, and aggregated HGG revealed that only the monomer could induce tolerance in Th. Monomeric HGG was also shown to induce tolerance in an antigen-specific manner. Th reactive to HGG could be tolerized by monomeric HGG, but not Th reactive to FGG or OVA. Helper function of Th was also shown to be antigen specific in that HGG-reactive Th helped only HGG-primed B cells. Certain HGG-specific Th clones were found to be refractory to tolerization with monomeric HGG, whereas other clones derived from the same uncloned cell line were tolerizable.

Animals↗

Long-term suppressor cell lines. I. Demonstration of suppressive function.

Suppressor T cell (Ts) lines have been generated and maintained in culture for over one year. Cells from these lines suppress proliferation by primed lymph node cells and antibody production by primed spleen cells. Ts were originally obtained from either spleens of mice rendered tolerant to human gamma globulin (HGG) or short-term cultures of normal spleen cells. Ts from these two sources have previously been shown to exhibit antigen specificity in that only HGG-specific immune responses were suppressed. Prolonged culture of Ts, however, leads to 2 events: an enrichment for suppressive activity in the cultures; and a polyclonal activation of Ts which is demonstrated by the acquired ability of Ts cell lines to regulate responses to antigens other than HGG. Ts cell lines still contain HGG-specific Ts which can be isolated by their capacity to bind to HGG-coated plates. Only HGG-specific immune responses are suppressed by the HGG-binding Ts.

Animals↗

Long-term suppressor cell lines. II. Suppressor-target interactions.

Long-term nonhybridized murine suppressor T cell (Ts) lines, some of which have been in culture for over one year, are genetically restricted in their ability to suppress proliferation of primed lymph node cells (LNC). The genetic restriction maps to the I region of the major histocompatibility complex and resides in either the I-A, I-E or I-J locus. Suppressive activity is only slightly decreased following irradiation of the Ts with 2000 rds. The target for suppressive activity expressed by Ts cell lines is the helper T cell as suggested by experiments in which LNC proliferation was maximally suppressed when Ts were present early in the assay culture. The identity of the target cell was confirmed by experiments in which Ts were shown to suppress the anti-human gamma globulin plaque-forming cell response resulting from co-culture of primed B cells with cloned human gamma globulin-specific helper T cells.

Animals↗