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Biomedical subjects

T Diamantstein

Publications and source records attributed to T Diamantstein.

At least 199 records · Page 11Linked to original sources

Chitin: an immunological adjuvant and a polyclonal B-lymphocyte activator.

Chitin, a linear beta 1-4 linked poly-N-acetylglucosamine, enhanced the in vivo immune response of normal mice to sheep red blood cells, but not that of mice with thymic aplasia (nude mice). The compound is mitogenic for murine B lymphocytes but not for thymocytes or splenic T lymphocytes. Similarly to well-known polyclonal B-lymphocyte activators; e.g. lipopolysaccharide, chitin induces differentiation of B lymphocytes into antibody-forming cells in vitro.

Adjuvants, Immunologic↗

Lymphoblastogenesis stimulates proliferation of interacting Lyt1 T cells in a syngeneic system.

The intravenous transfer of polyclonally activated lymphoblasts elicited a proliferative response of host-derived Lyt1 T cells in the spleens of syngeneic recipient mice. These Lyt1 T cells (responding in vivo to a syngeneic lymphoblast graft) stimulated proliferation of resting, syngeneic splenic Lyt1 T cells, derived from uninjected mice, in a one-way syngeneic mixed lymphocyte culture in vitro. The data are discussed in the context of T cell activation induced by lymphoblastogenesis in a syngeneic system.

Animals↗

Self-reactive T cells. IV. Self-reactive T cells induce polyclonal differentiation of IgM-producing B cells in vivo and in vitro.

Intravenous injection of lymphoblasts (generated in vitro by different T- or B-specific mitogens) induced a polyclonal activation of IgM-producing B cells in vivo in the spleens of syngeneic recipient mice. This polyclonal differentiation of host-derived B cells to IgM-producing plaque-forming cells was stimulated by host-derived self-reactive T cells activated in the splenic lymphoid cell population in response to the syngeneic lymphoblast graft. We found a stable factor in the supernatants of cultures of proliferating self-reactive T cells that induced (antigen-independent) polyclonal maturation, but not proliferation of IgM-producing B cells.

Animals↗

Self-reactive T cells. V. T cell-mediated suppression of B cell responsiveness to LPS.

The intravenous injection of polyclonally activated lymphoblasts elicited a proliferative T cell reaction in the spleens of syngeneic recipient mice. In the non-fractionated cell populations obtained from these spleens 6 days after lymphoblast transfer, the LPS-induced proliferation and differentiation of B cells in vitro was suppressed. This suppressive effect was mediated by T cells, as i) treatment with anti-Thy-1 antiserum plus complement restored responsiveness of B cells to LPS in the spleen cell population that had responded in vivo to a syngeneic lymphoblast graft, and ii) the responsiveness of B cells to LPS was not impaired in non-fractionated spleen cell populations of nu/nu mice injected with syngeneic lymphoblasts. The relationship of this nonspecific T suppressor cell activity to the previously described non-specific T helper cell activity for B cell activation is discussed.

Animals↗

Interaction between Entamoeba histolytica and the immune system. I. Mitogenicity of Entamoeba histolytica extracts for human peripheral T lymphocytes.

The effect of Entamoeba histolytica extracts (E.h.e.) on proliferation in vitro of human peripheral blood lymphocytes, cord blood lymphocytes, and lymphocytes enriched for T cells or non-T cells was investigated. As tested by 3H-thymidine uptake and by morphologic criteria, E.h.e. stimulate T lymphocyte proliferation. Non-T lymphocytes do not respond to E.h.e. The response of lymphocytes to E.h.e. differed from their response to Con A in several respects, indicating either that E.h.e. and Con A act on different subsets of T cells or that E.h.e. act by different mechanism on the Con A reactive cells.

Dose-Response Relationship, Immunologic↗

Direct in vitro evidence for different susceptibilities to 4-hydroperoxycyclophosphamide of antigen-primed T cells regulating humoral and cell-mediated immune responses to sheep erythrocytes: a possible explanation for the inverse action of cyclophosphamide on humoral and cell-mediated immune responses.

Suppressor T cells of humoral immune responses, effector T cells mediating DTH, suppressor T cells of DTH, and helper T cells of humoral immune responses, all with specificity to SRBC, were produced in mice. The biologic activity was tested in adoptive transfer experiments. In vitro treatment with different doses of 4-hydroperoxycyclophosphamide (4-HPCy) yielded the result that the various activities tested were not uniformly sensitive to the action of this drug: Suppressor T cells of humoral immune responses and effector T cells mediating DTH were resistant to doses of 4-HPCy that eliminated the activities of suppressor T cells of DTH and helper cells of the humoral immune response. These findings help to explain the various effects cyclophosphamide has on the in vivo immune response and may help to form a basis for the rational manipulation of the immune response by drugs that selectively affect different subgroups of immune cells.

Animals↗

Studies on T-lymphocyte activation. I. Is competence inductions in thymocytes by phorbol myristate acetate, an accessory cell-independent event?

The effect of phorbol myristate acetate (PMA) on lectin-induced murine thymocyte activation was studied. PMA itself failed to stimulate thymocyte proliferation, but potentiated concanavalin A (Con A)-induced thymocyte activation. A brief incubation of thymocytes with PMA changed the responsiveness of these cells to an optimal mitogenic dose of Con A present during the entire subsequent culture period. Further studies showed that PMA induced in a dose-dependent way within 30 min. an optimal competence of thymocytes to respond to the T-cell growth factor interleukin-2 (IL-2). In contrast to lectin-triggered competence induction, PMA-triggered induction of competence in thymocytes seemed to be independent of accessory cells.

Animals↗

Interleukin-2 allows in vivo induction of anti-erythrocyte autoantibody production in nude mice associated with the injection of rat erythrocytes.

Mice injected with rat red blood cells developed anti-erythrocyte autoantibodies detectable by a direct Coombs' test. Nude mice injected with rat red blood cells did not develop a Coombs-positive state, but nude mice injected with rat red blood cells plus the T cell helper factor, interleukin-2, produced autoantibodies to autologous mouse erythrocytes. The simultaneous injection of rat red blood cells and allogeneic spleen cells induced an early and vigorous autoantibody response in athymic nude mice as well as in euthymic control mice. These results are interpreted as indicating the possibility of an interleukin-2-stimulated in vivo differentiation (or clonal expansion) of helper T cells in nude mice in response to heterologous erythrocytes which could mediate an autoimmune B cell response.

Animals↗

"Self-reactive" T cells. I. In vivo reaction of T cells to transferred polyclonally activated syngeneic and autologous lymphoblasts.

Polyclonally activated splenic lymphocytes (generated in mitogen-stimulated cultures) were transferred to syngeneic or autologous recipient mice. Injection of cells into the footpad of syngeneic recipients induced a regional response in the ipsilateral popliteal lymph node; intravenous cell transfer elicited a systemic splenomegaly reaction. These reactions displayed a linear log number of transferred cells/response relationship in syngeneic and autologous systems. The kinetic and magnitude of the regional response to syngeneic lymphoblasts ands to allogeneic spleen cells were comparable. No difference was apparent in the phenomenology of the in-vivo responses to syngeneic lymphoblasts induced by various T- or B-cell mitogens. The in-vivo response was: 1. stimulated by large-size lymphoblasts; and 2. mediated by host T cells. Data excluded a direct involvement of mitogen or heterologous serum constituents in tissue culture medium in the described reaction. Experimental evidence argues against the involvement of virus components in the observed phenomenon.

Animals↗

"Self-reactive" T cells. II. Transferred syngeneic lymphoblasts induce T "stimulator" cells in vivo, to which syngeneic T cells "respond" in a syngeneic MLC in vitro.

Splenic T cells, engaged in an in-vivo "response" to transferred syngeneic lymphoblasts, displayed an extensive proliferative activity if cultured in vitro. These cells (blocked by mitomycin C) were "stimulator" cells in a one-way syngeneic mixed lymphocyte culture (S-MLC). "Responder" cells were derived form spleens of syngeneic (sex and age matched) mice. Fractionation studies showed that "stimulator" and "responder" cells in the investigated S-MLC were nylon-wool non-adherent and sensitive to treatment with anti-Thy-1 antiserum and complement, i.e. were cells of the T lineage. Coculture experiments demonstrated that direct cell contact is required to trigger a proliferative "response" in the S-MLC. Fetal calf serum-supplemented tissue-culture medium supported "responder" cell proliferation, normal mouse serum-supplemented medium did not. The in-vivo generation of a T-cell population, which could "stimulate" a syngeneic T-cell "response" in the S-MLC in vitro, was investigated.

Animals↗

"Self-reactive" T cells. III. In vitro restimulation of T cells, "responding" in vivo or in vitro to syngeneic lymphoid cells.

Polyclonally activated lymphoblasts, transferred to syngeneic recipient mice, elicited a host T-cell-mediated "response" in vivo. These T cells, which "responded" in vivo to syngeneic lymphoblasts (i.e. in vivo primed "responder" T-cell population), acquired the capacity to "stimulate" a "response" of syngeneic T cells in vitro in a syngeneic one-way mixed lymphocyte culture, S-MLC (i.e. in vitro primed "'responder" T-cell population). We now describe the presence of memory and specificity in these two types of "self-reactive""responder" T-cell populations. This is investigated in in vitro "restimulation" experiments with mitomycin-blocked syngeneic and allogeneic lymphoid cells of various origin. "Self-reactive" T cells could be restimulated repeatedly (over many weeks) with mitomycin-blocked syngeneic lymphoid-cell populations, but not with mitomycin-blocked allogeneic normal spleen cells. "Self-reactive" T cells "responded" to syngeneic large activated lymphoblasts, as well as to syngeneic small resting lymphocytes. We found no "responder" T-cell reactivity specific for the mitogen that induced syngeneic "stimulator" cell populations. Both populations of "self-reactive" T cells displayed reactivity to mitogen-induced allogeneic lymphoblasts.

Animals↗

Mitogenicity of Entamoeba histolytica extracts for murine lymphocytes.

Aqueous extracts or aqueous extracts of delipidated Entamoeba histolytica (E.h.e.) contain a mitogenic principle for murine lymphocytes. As detected by [3H]-thymidine incorporation and blast transformation, E.h.e. acted predominantly on T cells of splenic origin, but not on thymocytes or bone marrow cells. Furthermore, E.h.e. induced proliferation of a subset of non-T-cells which is present in the spleen of athymic nude mice, adhered to nylon wool, but could not be activated to produce antibody. It seems possible that polyclonal activation of lymphocytes by E. histolytica might play a role in the disturbance of the immune system as manifested in the impaired cell mediated immune response of E. histolytica infected hosts.

Animals↗

Relative susceptibilities of T cell subsets involved in delayed-type hypersensitivity to sheep red blood cells to the in vitro action of 4-hydroperoxycyclophosphamide.

4-Hydroperoxycyclophosphamide, a derivative of cyclophosphamide, in aqueous solution yields 4-hydroxycyclophosphamide, which acts on lymphocytes in vitro. This compound was employed to determine the relative susceptibilities of T cell subsets involved in delayed-type hypersensitivity to sheep red blood cells in vitro. The following ranking order could be established: precursors of suppressor T cells > antigen-activated suppressor T cells > T cells mediating DTH. These data provide direct in vitro evidence that the enhancement of the cellular immune response to sheep red blood cells by cyclophosphamide is due to selective inactivation of suppressor T cells or their precursors, respectively.

Animals↗

T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide.

As measured by [(3)H]thymidine uptake, spleen cells of mice injected 7 d previously with a single dose of cyclophosphamide (Cy) (125 mg x kg (-1)) gave an enhanced response to dextran sulfate (DS), a diminished response to lipopolysaccharide (LPS), and a normal response to concanavalin A. Addition of syngeneic thymocytes to spleen cells inhibited the enhanced response of the cells to DS and slightly enhanced their response to LPS. Pretreatment of thymocytes by 4-hydroxyperoxycyclophosphamide (4HP-Cy) in vitro (an in vitro active derivative of Cy) abrogated the effect of thymocytes on the DS response but not on the LPS response. Pretreatment of spleen cells by small doses of 4HP-Cy (0.1-1.0 mug. ml(-1)) in vitro enhanced the capacity of the cells to respond to DS but either did not affect, or even diminished their capacity to respond to LPS. The enhancement of the DS response by 4HP-Cy treatment could not be detected using spleen cells depleted of T cells or lacking functioning T cells. 4HP-Cy doses more than 3 mug ml(-1) diminished or abolished the capacity of the spleen cells to respond to LPS as well as their capacity to respond to DS. The results show (a) that in contrast to the LPS-reactive B-lymphocyte subset, the proliferative capacity of DS-reactive subset is negatively controlled by a Cy- and 4HP-Cy-sensitive T-cell subset and (b) that these T- suppressor cells are more sensitive to Cy and 4HP-Cy (to their respective active alkylating metabolites) than B lymphocytes and T cells carrying other immunological functions.

Animals↗

Effects of cadmium on the immune system of mice.

Chronic oral exposure of mice to Cd++ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd++ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd++ exposure alters the immune system of mice.

Animals↗