PubMed Health⌕ Search

Biomedical subjects

R K Gershon

Publications and source records attributed to R K Gershon.

At least 19 recordsLinked to original sources
PubMed1979

Genetic control of immunoregulatory circuits. Genes linked to the Ig locus govern communication between regulatory T-cell sets.

Antigen-stimulated Ly1:Qa1+ cells induce a nonimmune set of T-acceptor cells (surface phenotype Ly123+Qa1+) to participate in the generation of specific suppressive activity. The experiments reported here were designed to test the possibility that the interaction between T-inducer and T-acceptor cells might be governed by genes linked to the Ig locus. We find that inducer:acceptor interactions occur only if the inducer and acceptor T-cell sets are obtained from donor that are identical at the Ig locus and are independent of the Ig locus expressed on the B cells used for assay of T-helper activity. In addition, experiments using inducer and acceptor T cells from the congenic recombinant BAB. 14 strain show that T-T interactions are not governed by Ig-CH genes, per se. These data indicate that T-inducer: T-acceptor interactions are governed by Ig-linked genes that may control expression of VH-like structures on T cells, or control expression of as yet unidentified cell-surface molecules.

Animals↗
PubMed1979

Ontogeny of cells involved in the suppressor circuit of the immune response.

Some macrophage (M phi) cell surface structures which bind T cell-derived factors remain intact after the M phi are killed by heating at 56 degrees C (but not 72 degrees C) for 45 min. As a result, appropriately killed M phi (HK M phi) can act as competitive antagonists for those M phi functions which are involved in binding and active presentation of T cell-derived regulatory signals. By blocking the transmission of these signals with HK M phi, we have found that the spleens of newborn mice contain considerable numbers of "latent" helper cells whose activity is not ordinarily seen because it is overridden by suppressor mechanisms. Similarities between these neonatal helper cells and a subset of adult T helper "inducer" cells (cell surface phenotype Ly-1+; Ly-2-, 3-; IJ+; Qa 1+), whose activity appears in significant numbers only after immunization, are described.

Animals↗
PubMed1979

Induction of suppressor cells in rat spleen: influence of microbial stimulation.

The role of the products of prostaglandin synthetase in the suppression of in vitro secondary antibody responses by rat spleen cells was examined. By including cells from both germfree and conventional rats in these studies, the effect of in vivo microbial stimulation on this suppression was also determined. We found that 1) the suppression that is normally present in the spleen cells of rats can be eliminated by the use of glass wool or indomethacin; 2) germfree rats do not display this suppressor activity, and 3) this "deficit" in the germfree rat may be due to a lack of a microbial-induced signal from a nonadherent cell to an adherent prostaglandin-containing macrophage, implying that at least two cells are involved in the prostaglandin-synthetase dependent suppressor effect. It is possible that large amounts of some or all microbial products activate "suppressor" macrophages and that inbred rats behave like "chronically infected" mice because of an inability to regulate their "normal" microbial flora.

Animals↗
PubMed1979

Antigen-binding T cells: dose response and kinetic studies on the development of different subsets.

We have described a number of the parameters involved in the in vitro induction of specific SRBC-binding T cells (T rosette-forming cells, T-RFC). Although T-RFC precursors pass through nylon, most of the induced cells do not; nor do detectable numbers of Ly 1+2, 3- cells bind antigen with sufficient stability to form rosettes. The ratio of Ly 2,3:Ly 1,2,3 T-RFC varies with time after immunization and with the dose of antigen used for stimulation. Relatively high or low doses of antigen selectively induce Ly 1,2,3 T-RFC. Ly 2,3 T-RFC, when they appear, follow Ly 1,2,3 T-RFC. Pretreatment of T cells with anti-Ly sera before RFC induction prevents formation by Ly2+ T-RFC. Since anti-Ly 1 treatment blocks RFC formation and since Ly 1,2,3, T-RFC always precede the appearance of Ly 2,3, T-RFC, our results suggest that some Ly 1+ cells (Ly 123 at least, but perhaps also Ly 1) may act as inducers, precursors, and/or amplifiers for Ly 2,3 RFC as they appear to do for Ly 2,3 suppressor and killer cells. Thus, our results confirm and extend the observed similarities between T-RFC and other Ly 2+ cells such as killer and suppressor cells as well as their differences from Ly 1+ helper cells.

Animals↗
PubMed1979

Immunoregulatory circuits among T cell sets: effect of mode of immunization on determining which Lyl T cell sets will be activated.

Lyl T cells are able to induce B cells to make antibody and also to induce a resting Lyl23 T cell set to exert potent feedback suppression. Which of these two pathways Lyl T cells take can be influenced by the mode of immunization. In particular, in vitro immunized Lyl T cells are more likely to induce suppression than are Lyl T cells immunized in vivo even when both populations deliver the same amount of help to purified B cells. The feedback suppression induced by the Lyl T cells immunized in vitro can be distinguished from suppression mediated by Ly2+ T cells; in the former case suppression is preceded by a precocious antibody response, whereas suppression mediated by Ly2+ T cells is apparent throughout the entire period of observation.

Animals↗
PubMed1978

Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition.

Purified Ly1 cells induce other T-cell sets to exert potent feedback inhibitory activity and this T-T interaction has been shown to play an important role in regulating in vivo immune responses. Approximately 2/3 of Ly1 cells also express the Qa1 surface phenotype (Ly1:Qa1+ cells). The experiments reported here indicate that Ly1:Qal+ cells are responsible for induction of feedback inhibition and that signals from both Ly1:Qal+ cells and Ly1:Qal- cells are required for optimal formation of antibody by B cells.

Animals↗
PubMed1978

Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets.

We have examined the ability of macrophages (Mphi) to transmit T-cell derived suppressor signals to other T cells. The suppressor signal studied is an antigen-specific factor which suppresses the ability of adoptively transferred, sensitized lymphocytes to express contact hypersensitivity in normal recipients. We have found that this factor binds to peritoneal exudate Mphi via cell surface structures which can be blocked with heat-aggregated gamma globulin. Dead (HK) Mphi bind the factor but fail to present it in a functional way to assay (immune) T cells, whereas live (L) Mphi perform both functions. Further, L Mphi can retrieve the factor in an active form from the surfaces of HK Mphi. Based on these and other findings (1-5), we discuss the possibility that Mphi may play as important a role in presenting T-cell communication signals to the cells of the immune system as they do in presenting antigen.

Animals↗
PubMed1978

Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition.

These experiments test the hypothesis that cells carrying the Ly1+23- surface phenotype are programmed exclusively for helper and not suppressive activity regardless of external conditions such as the mode or type of antigen stimulation. To this end, we have stimulated purified populations of Ly1 cells with antigen in vitro using conditions devised to induce unselected T cells to express optimal levels of antigen specific T-suppressor activity. We find that after such stimulation, Ly1 cells generate SRBC-specific T-helper activity but not T-suppressive activity. These findings establish that the Ly1.2+,2.2/3.2- surface phenotype is a stable, and probably invariant, marker of T cells that are programmed to express only helper activity and have lost the capacity to directly suppress the antibody response. These findings support the concept that the genetic program for a single differentiated set of cells combines information for cell surface phenotype and function. We also demonstrate that antigen-stimulated Ly1 cells, in addition to inducing B cells to secrete antibody, can induce or activate other sets of resting T cells to develop profound suppressive effects. The surface phenotype of this feedback suppressive T-cell set is shown to be: Ly1+2+3+Qa1+. These findings, taken together, indicate that activation of resting Ly123 cells by immune Ly1 TH cells may represent an important homeostatic immunoregulatory mechanism.

Animals↗
PubMed1978

Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice.

We have shown that (a) purified T-helper cells induce cells of another T-cell set-, expressing the Ly123+Qa1+ surface phenotype, to exert potent suppressive activity, (b) this T-T interaction plays an important role in regulating in vivo immune responses, and (c) this interaction represents an important barrier to protocols intended to augment the immune status of individuals by adoptive (or active) immunotherapy. Our results also indicate that the Ly123+ T-cell set mediating feedback suppression in vivo is sensitive to both low doses of cyclophosphamide and removal of the thymus in adult life. The importance of this T-T interaction to normal, physiologic regulation of the immune system is emphasized by the finding that the major T-cell deficit of NZB mice (an inbred strain of mice that spontaneously develops an autoimmune disorder) is the absence or malfunction of an Ly123+ T-cell set responsible for feedback inhibition.

Animals↗
PubMed1978

Association of defective feedback suppressor T cell activity with autoimmunity in NZB mice.

A "feedback suppressor T cell" highly dependent on signals from Ly 1 T helper cells for activation is described. The signal from the Ly 1 cell binds to Fc-like receptors on macrophage membranes. The feedback suppressor cell expresses all three Ly antigens as well as the Qa 1 antigen on its surface, is very sensitive to low doses of cyclophosphamide, disappears relatively rapidly after adult thymectomy, and cannot be demonstrated in NZB mice 6 weeks or older.

Age Factors↗
PubMed1978

Molecular identification of a surface structure on B cells (Lyb-3) and its relationship to B cell triggering.

Lactoperoxidase-catalyzed radioiodination of cell surface proteins and immunochemical procedures are used to identify murine splenic lymphocyte membrane components bound by anti-Lyb-3 serum. This antiserum defines membrane components (Lyb-3) on a subpopulation of murine B cells that may function as a receptor for T cell signals. SDS-PAGE analysis of surface-labeled membrane components bound by anti-Lyb-3 serum demonstrated a single molecular species of 68,000 d. The polypeptides recognized by anti-Lyb-3 are not composed of disulfide-linked subunits and bear no antigenic relationship with known membrane immunoglobulins (IgM or IgD). Absorption of anti-Lyb-3 serum with the 68,000 d polypeptides removed the ability of anti-Lyb-3 serum to augment the in vivo immune response of mice to low doses of sheep erythrocytes. The latter provides formal proof that the 68,000 d polypeptide bound by anti-Lyb-3 serum is the target on the B cell membrane for the immunoenhancing activity of the antiserum.

Animals↗
PubMed1978

Regulation of delayed-type hypersensitivity reactions by cyclophosphamide-sensitive T cells.

The onset, intensity, and duration of DTH reactions elicited in mice immunized with either SRBC or products of the major histocompatibility complex can be altered significantly by pretreatment with CY 1 to 2 days before immunization. Such drug pretreatment tends to augment low DTH responses caused by the use of too much antigen and to diminish many responses that are optimal. Thus, pretreatment with CY does not specifically eliminate suppressor cells. Our results are most consistent with the notion that the cellular targets of low doses of CY are positive and negative feedback regulatory cells, which may consist of one population with two effects or, more likely, two distinct cell populations.

Animals↗
PubMed1978

The evolution of immunosuppressive cell populations in experimental mycobacterial infection.

Immunosuppressor activity of considerable potency and complexity was generated during the course of chronic, progressive infection of C3H/Anf mice by Mycobacterium lepraemurium. From the 5th through 10th week after inoculation, spleen cells from infected mice mildly but reproducibly suppressed the direct plaque-forming cell response of normal spleen cell cultures to sheep erythrocytes. Suppression at this stage of infection was mediated by cells with macrophage-like characteristics. A marked increase in splenic suppressor activity at 10 to 11 weeks was associated with the appearance of a second suppressor cell subpopulation composed of T lymphocytes. The appearance of these cells was closely related in time to the onset of rapid splenic enlargement and a loss of cutaneous delayed type hypersensitivity to antigens of M. lepraemurium in mice at 10 to 11 weeks of infection. Suppressor cells were not present in peripheral lymph nodes until terminal infection at 22 to 25 weeks. Suppressor spleen cells depressed the T-dependent antibody response most severely, but there was also a direct effect upon B cells as shown by moderate suppression of responses to TNP-LPS and DNP-Ficoll. Spleen cells from 14-week-infected mice generated a soluble suppressor factor(s) that induces depression of moderate severity, however, the immunosuppression by intact cells was far greater.

Animals↗
PubMed1977

Nylon adherent antigen-specific rosette-forming T cells.

Shortly after intravenous immunization of mice with heterologous erythrocytes (RBC) antigen-specific Thy 1+ cells which form rosettes with the immunizing RBC (thymic-derived lymphocytes-forming rosettes [T-RFC]) appear in the spleen. These T-RFC are much less stable than Thy 1- RFC (non-thymic-derived [B-RFC]) although most if not all of both classes of RFC adhere to nylon. T-RFC are induced with low doses of antigen (which fail to induce B-RFC) and are inhibited by higher antigen doses which are optimal for induction of B-RFC. Pretreatment of mice with cyclophosphamide prevents the high dose inhibition of T-RFC. Although there are many parallels between the production of T-RFC and delayed-type hypersensitivity (DTH) it is unlikely that the T-RFC are essential for DTH reactions since DTH can be transferred with cells which pass through nylon, and such cells are almost totally depleted of T-RFC. Thus immunization can lead to the production of large numbers of antigen-specific T-RFC whose functional role in the immune response is unknown. However, the characteristics of the T-RFC suggest that they may play an important role in amplification of suppressor cell activity.

Animals↗
PubMed1977

Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice.

CBA/N mice have an X-linked B-cell maturation defect which is reflected in part in an absence or dysfunction of a subclass of mature B cells. We have immunized the defective male offspring of the mating (CBA/N female X BALB/c male) with BALB/c spleen cells. The resulting antiserum (alphaLyb3) selectively reacts with a component on the surface of a portion of B cells from a panel of H-2 different mouse strains. Binding of alphaLyb3 serum to this B-cell subclass results in substantial (10- to 20-fold) enhancement of the antibody response to low doses of SRBC. Both binding and enhancing activity are removed by absorption with B cells from B6 and BALB/c, but not CBA/N mice. Absorption of the serum with bone marrow cells, T cells, or thymocytes from Lyb3+ strains does not remove activity. Since the enhanced plaque-forming cell (PFC) responses are specific for the immunizing antigen, and since no PFC response is produced by injection of the antiserum alone, this enhancement probably reflects a second signal produced by specific interaction between antibody and the surface Lyb3 component. Moreover, this signal can partially replace the requirement for T cells in the production of antibody to a "thymus-dependent" antigen. These findings (taken in conjunction with the previously described immune defects in CBA/N mice and other studies of B-cell maturation) suggest to us that Lyb3 is a cell surface component expressed selectively on a mature B-cell subclass. This component is important in B-cell triggering by antigen and fails to develop in CBA/N mice, due to a dysfunction of a regulatory gene on the CBA/N X chromosome.

Animals↗