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T Maier

Publications and source records attributed to T Maier.

At least 73 records · Page 4Linked to original sources
PubMed1987

Natural suppressor (NS) activity from murine neonatal spleen is responsive to IFN-gamma.

Natural suppressor (NS) cell activity is the ability of apparently unprimed "null" cells to nonspecifically suppress immune responses. Previously we have shown that NS cell activity from the spleens of mice undergoing chronic graft-vs-host disease (GVHD) is enhanced in vitro by activated T cell signals (e.g., Con A supernatant [CAS]). Here we asked if the naturally occurring suppressor activity found in the neonatal mouse spleen is caused by NS cells, and if so whether this NS activity is also responsive to T cell signals. Finally, we wanted to identify the material in the CAS to which the NS cells respond. Spleen cells from (BALB/c X B10.D2)F1 neonates contain potent, genetically unrestricted suppressor activity toward normal mitogen responses. The cells responsible for this suppression are nonadherent, Thy-, Ig- and are thus by definition NS cells. Neonatal spleen NS cells suppress the indicator Con A response of all mouse strains tested, but their behavior with regard to LPS responses is different. They significantly inhibit the indicator LPS response of allogeneic strains, but are less inhibitory of LPS-stimulated syngeneic (BALB/c X B10.D2)F1 and parental strains. However, the addition of CAS to these latter cultures enhances the NS inhibition of the LPS response to the level of suppression seen with a Con A response. Two lymphokines were able to replace the CAS. Recombinant interferon-gamma (rIFN-gamma) closely mimics the activity found with whole CAS, with low concentrations (1 U/well) being capable of enhancing the neonatal NS activity to near-maximal levels. Recombinant interleukin 2 (rIL 2) is also capable of stimulating the neonatal NS activity to near maximum. However, the rIL 2 must be added at much higher concentrations, taking greater than 50 U/well to get maximum activation of NS suppression. The addition of anti-IFN-gamma antiserum to these LPS suppression assays removes the ability of CAS to activate the neonatal NS cells. Anti-IFN-gamma antiserum also removes the ability of rIL 2 as well as rIFN-gamma to activate the NS cells. It thus appears that the rIL 2 is working by its ability to stimulate IFN-gamma production. Anti-IFN-gamma also removes the ability of the neonatal NS cells to suppress a Con A response. Therefore, it appears that neonatal splenic NS cells respond to, and are activated by, IFN-gamma to carry out their suppressive activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Memory for spatial and temporal order in aphasics and right hemisphere damaged patients.

Sets of five photographs per item were presented successively in five vertically arranged frames to 53 aphasics, 27 right hemisphere damaged (RHD) patients and 18 normal subjects. Following the presentation of the five slides subjects were given a spatial and a temporal recognition task. In the spatial task subjects had to indicate which of two pictures of a probe had been nearer to the top of the vertically arranged set of frames. In the temporal task they had to indicate which of the two pictures of the probe had been presented earlier. Aphasics made significantly more errors than RHD and normals in both the spatial and the temporal task, while RHD were significantly impaired in comparison to the normal controls only in the spatial task.

Adult↗
PubMed1986

Natural suppressor activity in graft-vs-host spleen and normal bone marrow is augmented by IL 2 and interferon-gamma.

Natural suppressor (NS) cells isolated from the spleens of mice 34 or more days after induction of chronic graft-vs-host disease showed potent suppressor activity that was dependent on the presence of lymphokines such as those found in lectin-free Con A supernatant (CAS). Both IL 2 and IFN-gamma were found to enhance NS activity, with IFN-gamma being the most active molecule. To generalize these findings, normal adult bone marrow (BM), a second environment where NS activity has been reported, was examined. Normal adult BM cells nonspecifically suppressed both B and T cell mitogen responses. BM suppression could also be enhanced by the addition of CAS to the cultures. Removal of plastic-adherent cells, Thy-1.2-positive cells, or B cells did not significantly diminish suppression or remove the ability to enhance suppression with CAS. When isolated on discontinuous Percoll gradients, BM suppressor cells banded in the less dense fractions, and the suppression in these bands was also enhanced by lymphokines. The suppressive activity of these cells was greatly enhanced by the addition of CAS, IFN-gamma, or IL 2. However, IFN-gamma appears to be a more potent enhancing molecule, being active at levels between 1 and 10 U/ml.

Animals↗
PubMed1986

Comparative evaluation of New York City and modified Thayer-Martin media for isolation of Neisseria gonorrhoeae.

Commercially manufactured New York City (NYC) medium and modified Thayer-Martin (MTM) medium were compared for their ability to isolate Neisseria gonorrhoeae from clinical specimens. Twenty-seven public health laboratories throughout California evaluated 4,802 specimens collected from patients attending either sexually transmitted disease or family planning clinics. Total of 726 and 737 N. gonorrhoeae isolates were recovered from NYC and MTM medium, respectively. Although less contamination was noted on NYC medium, MTM medium was equivalent to commercially prepared NYC medium for the isolation of N. gonorrhoeae from clinical specimens.

Cervix Uteri↗
PubMed1985

Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells.

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.

Animals↗
PubMed1985

Preliminary characterization of a soluble immunosuppressive molecule from DBA/2 spleen cells using monoclonal antibody immunoadsorbence.

In a previous publication a monoclonal antibody (B16G) which appeared to recognize T suppressor cells and a T-suppressor factor (TsF) in the spleens of DBA/2 mice was described. B16G appears to be directed to a public specificity of DBA/2 TsF and therefore has been shown to inhibit a variety of immunological reactions. The present study involves preliminary characterization of the material with which B16G reacts. It was found that the B16G-reactive protein (putative TsF) could be absorbed and eluted specifically from a B16G immunoadsorbent column. Material eluting from the B16G column reacted with B16G in an ELISA and appeared to run as two or more bands of 40-45 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The eluted material was biologically active (i.e., suppressive) in the standard assay (mixed leukocyte reaction of DBA/2 splenocytes with B10.BR targets), and its suppressive activity was abrogated by the addition of B16G to the mixed leukocyte reaction cultures. Sephadex G-150 chromatography of the B16G-reactive material showed that under these conditions, its native molecular mass was between 80-90 kDa, indicating that it might occur as a dimer under natural conditions.

Animals↗
PubMed1985

Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. I. Impairment of mitogen responses and suppressor phenomena.

In our laboratory, we have developed a murine model to examine GVHD across minor histocompatibility antigens. In our model, GVHD is induced by injecting B10.D2 spleen cells into irradiated BALB/c recipients. Seven to 10 days after irradiation and injection of cells, there are significant changes in cell function in the recipient spleens. In the B10.D2----BALB/c (600 rad) model, recipient spleen cells are profoundly unresponsive to Con A and LPS stimulation but show increased B cell activity measured by Staphylococcus aureus protein A plaque-forming activity. Spleen cells from such GVH mice profoundly suppress the mitogenic responses of normal BALB/c or B10.D2 spleen cells to Con A and LPS. The degree of impairment of the mitogenic response and the ability to suppress normal cells is proportional to the dose of cells used to induce GVH reactions. Both the inability to respond to mitogens and the capacity to suppress are also related to the dose of irradiation given to the recipients. In addition, immunosuppression across minor histocompatibility antigens shows an unevenhandedness. If we inject parental B10.D2 or BALB/c cells into F1 recipients (P----F1), there is greater inhibition of mitogenic responses when B10.D2 parental cells are given than when BALB/c cells are given to the irradiated F1 recipients. These experiments show that significant immunosuppression occurs during GVH reactions across minor histocompatibility barriers. The degree of suppression varies according to the dose of cells used to induce GVH, the dose of irradiation to the recipient and the "strength" of the GVH recognition system. Such experiments provide models for GVH disease seen in humans who receive treatment for leukemia or other diseases that involves recipient irradiation and infusion of HLA-identical bone marrow.

Animals↗
PubMed1985

Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity.

We explored the immunoincompetence of mice undergoing a chronic graft-vs-host reaction (GVHR) across minor histocompatibility barriers. BALB/c and B10.D2 mice are H-2d and mls b, and differ only with regard to minor histocompatibility antigens (MiHA). A large number of BALB/c mice were unirradiated or were irradiated with 300, 600, or 900 R. They then were injected with 5 X 10(7) spleen cells from either allogeneic B10.D2 or syngeneic BALB/c mice. The spleen cells from these recipient mice were assayed at various times post-irradiation/injection for their proliferative response to Con A and LPS, their ability to suppress the mitogen responses of normal spleen cells, and for the genetic specificity of this suppression. Spleen cells from BALB/c mice that had received 600 or 900 R (but not 0 or 300 R), and allogeneic B10.D2 lymphocytes, became very hyporesponsive to mitogens and became suppressive in vitro by days 7 to 10 post-irradiation/injection. These phenomena persisted for the entire 49 days of the experiment. After an initial period of splenomegaly, the spleens of these mice gradually became depleted of viable lymphocytes. Initial characterization of suppressor cells found in the spleens of GVH mice showed that they were not removed by treatment with anti-Thy-1.2 plus complement. GVH suppressors also were not adherent to plates coated with antiserum directed towards murine Ig. In addition, these cells did not adhere to plastic plates. Thus, we believe that the suppressor cells found in mice undergoing GVHD across MiHA are not mature T cells, B cells, or macrophages, but belong to a class of suppressor cells termed natural suppressor (NS). Genetic analysis of NS cell activity showed that as early as 10 days post-irradiation/injection, NS cells inhibited mitogen responses of all mouse strains tested, the exception being the relative difficulty in suppressing the LPS response of B10.D2 (syngeneic with donor cells). By day 42, this had developed into an almost complete inability to suppress a B10.D2 LPS response, although at this time NS cells were still capable of inhibiting all the other mitogen responses of all strains tested, including the Con A response of B10.D2 spleen cells. Moderate amounts of mitogen unresponsiveness and suppressor activity were seen in the syngeneic groups (BALB/c----BALB/c) but only if recipients received 600 or 900 R. This was a transient phenomenon that was maximal at day 14, and which we believe to be a similar but less severe degree of immunoincompetence when compared with that seen with allogeneic stimulation in the B10.D2----BALB/c GVH model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The molecular basis of T helper cell function--I. Allotype- and MHC-linked determinants on antigen-specific, H-2-restricted T cell lines, hybridomas and lymphomas.

A T-cell hybridoma clone, which produces antigen-specific helper factors and a T-cell lymphoma clone which produces non-specific helper factors was used to study the expression of T-cell allotypes and Ia antigens. Use was made of rabbit antisera against isolated T-cell receptor material and of monoclonal mouse antibodies against isolated rat Ia antigen. The rabbit antisera detected endogenously produced determinants both on the membrane and on intracellular polypeptides of these cells. The monoclonal mouse anti-rat-Ia antibodies detected polymorphic determinants on mouse Ia antigens and reacted with endogenously produced molecules on the membrane and on intracellular molecules of the hybridoma and lymphoma cells. The molecules carrying Tcr allotypes were single-chain polypeptides with mol. wts of 60,000-70,000 and the molecules carrying Ia-like antigenic determinants were single-chain polypeptides with mol. wts of 40,000-50,000. Thus T-cell allotypes and Ia antigens were found on separate polypeptide chains. The role and genetic localization of allotype-like and Ia-like molecules in T-cell products is discussed.

Animals↗
PubMed1983

Characterization of a monoclonal antibody directed to a T cell suppressor factor.

A monoclonal antibody raised by fusion of immune BALB/c splenocytes with NS1 cells is described. BALB/c mice were immunized with a T suppressor factor (TsF) raised in DBA/2 mice with specificity for the P815 tumor. The TsF had been purified by affinity chromatography before its use as an immunogen. The monoclonal antibody (B16G) was shown to affect the course of P815 growth in DBA/2 mice if administered i.v. on days -2 to 0 before tumor cell inoculation. Mice treated with B16G demonstrated slower tumor development and growth than controls, and a small number of animals (about 10%) did not develop tumors; all controls did. It was also shown that B16G did not exhibit total specificity for the P815 tumor in that it had similar effects on the growth of an unrelated myosarcoma (M-1) of DBA/2 mice. The general immunopotentiating effect of the B16G monoclonal was demonstrated by the fact that spleen cells of DBA/2 mice that had received B16G showed significantly higher MLC than did equivalent controls. When spleen cells of DBA/2 mice were depleted of B16G-reactive cells by panning in vitro, it was also found that cells so treated gave rise to elevated MLC reactions in comparison to appropriate controls. When an immunoadsorbent was prepared with B16G and cell lysates from splenocytes of immunosuppressed mice were passed over it, the immunosuppressive properties of the lysate in MLC were eliminated. The conclusion that the B16G recognizes a marker common to a group of regulatory T cells in DBA/2 mice is discussed.

Animals↗
PubMed1982

Anti-tumor effects of an antiserum raised in syngeneic mice to a tumor-specific T suppressor factor.

DBA/2 mice inoculated with either cells from the syngeneic P815 tumor or tumor cell membrane extracts develop T suppressor cells which suppress the in vitro generation of cytotoxic T lymphocytes with specificity for the tumor. A soluble suppressor factor with similar properties can be isolated from suppressor cell-enriched populations. It can be highly purified by appropriate immunoadsorption. Antisera to this suppressor factor raised in either DBA/2 or C57BL/6 mice can specifically absorb out suppressor factor and eliminate suppressor cells in the presence of complement. The in vivo effects of these antisera were tested for their ability to modulate the growth of P815 tumors in DBA/2 mice. It was found that the antiserum raised in syngeneic (DBA/2) but not allogeneic (C57BL/6) mice was able to significantly slow the rate of tumor growth and to prolong survival in treated mice. The antiserum was effective in this way only if it was administered early in the course of tumor growth. It was shown that this effect was not attributable to the presence in the serum of antibodies directed to antigens present on P815 cells, and it therefore appears to be due to interference with the function of T suppressor cells arising early in the immune response to the tumor cells.

Animals↗
PubMed1982

Cognitive impairments of aphasics in picture sorting and matching tasks.

On the basis of earlier experiments showing a differential deficit of aphasics in picture sorting and matching tasks, two experiments were conducted to test the conjecture of a specific deficit of aphasics in the analytical appraisal of individual features. Broca's and Wernicke's aphasics--according to clinical diagnoses and the Aachener Aphasie Test--were compared with patients having right-hemisphere lesions or left-hemisphere lesions without aphasia. Both groups of aphasics differed from the control groups in the sorting task, irrespective of the sorting criterion, but the differences were small. The picture matching task did not discriminate between groups. Obviously, the basic assumption has to be modified with respect to specific conditions of task requirements. The experimental literature is reviewed.

Aphasia↗