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Biomedical subjects

J Sprent

Publications and source records attributed to J Sprent.

At least 199 records · Page 11Linked to original sources
PubMed1977

The generation of killer cells to trinitrophenyl-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens.

Negatively selected mouse and rat lymphocyte populations, specifically deprived of alloreactivity to a particular major histocompatibility complex (MHC) haplotype, are nevertheless fully capable of responding to trinitrophenyl (TNP)-modified allogeneic stimulator cells and developing cytotoxic T-lymphocyte activity to TNP-altered allogeneic target cells. As for syngeneic systems, lytic expression of those responder killer cells also requires MHC identity between the target and stimulator cell populations. Such a finding argues strongly against two variations of the dual recognition hypothesis: like-like interactions and adaptive differentiation. Instead, these data favor either the altered self model or a third variation of the dual receptor model, where one of the relevent receptors is specific for the modifying antigen and the second is a low affinity receptor unable to be triggered in the absence of a modifying antigen.

Animals↗
PubMed1976

Helper function of T cells depleted of alloantigen-reactive lymphocytes by filtration through irradiated F1 hybrid recipients. I. Failure to collaborate with allogeneic B cells in a secondary response to sheep erythrocytes measured in vivo.

Helper T cells were obtained by injecting heavily irradiated semiallogeneic mice with lymph node cells from H-2-incompatible parental strain mice primed with sheep erythrocytes (SRC) 2 mo before. Thoracic duct lymphocytes collected from the recipents 18-40 h later (nearly all of which were theta-positive and of donor origin) were totally and specifically unresponsive against host-type determinants in mixed-lymphocyte culture. The filtered cells were transferred to irradiated semiallogeneic mice together with SRC and anti-theta-serum-treated (B) cells from SRC-primed syngeneic, semiallogeneic, or allogeneic mice. When antibody-forming cells were measured in the spleen 5-9 days later, effective IgM and IgG collaborative responses were observed with both syngeneic and semiallogeneic B cells but not with allogeneic B cells. No evidence was found that the failure to obtain collaboration with the allogeneic B cells was due to inhibition of the B cells by the T cells or vice versa.

Animals↗
PubMed1976

Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system.

When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed.

Animals↗
PubMed1976

Effect of recent antigen priming on adoptive immune responses. III. Antigen-induced selective recruitment of subsets of recirculating lymphocytes reactive to H-2 determinants.

Information was sought on the reactivity of thoracic duct lymphocytes (TDL) from parental strain mice injected intravenously with large numbers of irradiated semiallogeneic spleen cells. TDL collected at 1 day after spleen cell injection were almost totally depleted of lymphocytes able to produce cell-mediated lympholysis (CML), a graft-versus-host (GVH) reaction, and skin allograft rejection against the H-2 determinants on the injected spleen cells. Normal or near normal responses were observed against third-party determinants. In the case of CML, there was no evidence that the unresponsiveness was due to suppressor cells. In marked contrast, the capacity of TDL to exert a specific mixed lymphocyte reaction (MLR) against the injected determinants was reduced by no more than two to fourfold; this applied whether MLR were measured in vivo or in vitro. Injection of normal rather than irradiated semiallogeneic spleen cells gave similar results. Complete and specific removal of MLR-producing lymphocytes was achieved, however, in a different system in which parental strain T cells were filtered from blood to lymph through irradiated F1 hybrid mice. Since this system presumably provided a much higher concentration of H-2 determinants to the responding lymphocytes, it is suggested that the differing results obtained with these two systems may indicate that certain cells reactive to H-2 determinants are of low affinity, their reactivity being detected in the MLR, but not by other parameters. With both systems, MLR-producing lymphocytes reappeared in the lymph after 2-3 days; the cells collected at this stage gave an MLR of altered kinetics. The present data, in toto, suggest that under certain conditions of antigen presentation, virtually all recirculating lymphocytes reactive to a given set of H-2 determinants can be induced to leave the circulation for a period of 1-2 days. After responding to the injected determinants (presumably in organs such as the spleen), the cells re-enter the circulation in an activated state after 2-3 days.

Animals↗
PubMed1976

Specific adsorption of IgM antibody onto H-2-activated mouse T lymphocytes.

Evidence is presented to support the contention that IgM demonstrable by surface immunofluorescent staining on H-2-activated T cells represents specifically adsorbed B-cell-derived alloantibody. T cells activated to H-2 determinants expressed surface IgM only when the progenitor cell populations contained B lymphocytes. IgM was not detected on T cells activated to determinants which fail to stimulate alloantibody production (e.g., M-locus determinants). In addition, IgM-negative H-2 activated T cells (derived from B-cell-depleted lymphoid cells), unlike M-locus-activated T cells, adsorbed IgM in a specific manner when incubated in vitro with "early bleed" antisera raised against the activating H-2 determinants.

Adsorption↗
PubMed1976

Immunoglobulin turnover in B lymphocyte subpopulations.

"In vitro" turnover of leucine-labeled and of radioiodinated IgM has been studied with cells from various lymphoid organs of nude mice, i.e. lymph nodes, thoracic duct, spleen and bone marrow, as well as with subpopulations of B cells from spleen and bone marrow separated by free flow electrophoresis. Three types of IgM-producing lymphocytes could be distinguished by their turnover rates of IgM, by the size of the released IgM and by the capacity of the IgM molecules to be labeled by the lactoperoxidase-catalyzed radioiodination reaction and/or by incorporation of radioactive leucine. Type I cells release 7-8 S IgM rapidly (t1/2 = 1-3h); the released IGM is leucine-labeled and radioiodinated. Type II cells release 7-8 S IgM slowly (t1/2 =10-30); the released IgM is leucine labeled and radioiodinated. Type III cells release 19 S IgM rapidly (t1/2 =2-4 h); the released IgM is leucine labeled, but not radioiodinated. Lymph nodes and thoracic duct contain predominantly type II cells, bone marrow contains type I and II cells, spleen contains type I,II and III cells. It is suggested that type III cells are Ig-secreting plaque-forming plasma cells, type II cells are small, resting "memory" B cells, and type I cells may be newly formed antigen-inexperienced B cells.

Animals↗
PubMed1976

Activation of T lymphocytes to M locus determinants in vivo. I. Quantitation of T cell proliferation and migration into thoracic duct lymph.

Proliferative responses to M locus (Mls) determinants were investigated in vivo by injecting T cell-containing populations intravenously into irradiated H2-identical, Mls-incompatible mice. Responses were studied 1-6 days later by measuring levels of radioactivity in the spleen and lymph nodes of the recipient 45 min after intravenous injection of tritiated thymidine. High responses were observed against Mlsa and Mlsd determinants, i.e. determinants which give strong proliferative responses in vitro. With injection of thoracic duct lymphocytes (TDL), lymph node or thymus cells, the responses, both in the spleen and the lymph nodes, reached a peak at day 3-4 and then fell sharply. This was in marked contrast to the stimulation observed with H-2-incompatible mice where, with TDL or lymph node cells (though not with thymus cells), responses were low at day 3-4 but reached high levels at day 6. Significant responses were also observed against Mlsb and Mlsc determinants, i.e. determinants which stimulate poorly in vitro. The kinetics of this response differed from that against Mlsa or Mlsd determinants in in that proliferation was very low at day 4 but high at day 6. No evidence was found that the responses observed reflected "back-stimulation" by the host. Since congenic resistant strains were not used, the possibility that the stimulation observed was in fact due to minor transplantation antigens rather than Mls determinants could not be excluded. Large numbers of blast cells appeared in thoracic duct lymph of mice sustaining responses to Mlsa or Mlsd determinants. Nearly all of these cells had recently synthesized DNA and entered the lymph after day 3.

Animals↗
PubMed1976

Hemopoietic reconstitution obtained in F1 hybrids by grafting of parental marrow cells.

T-cell tolerance to CML and MLR determinants in tetraparental bone marrow chimeras, prepared by injecting lethally x-irradiated F1 hybrids with bone marrow cells from both parental strains, is most likely due to clonal deletion. Tolerance to CML, but not to the host's MLR, determinants is observed when lethally x-irradiated F1 hybrids are repopulated with bone marrow from one parental strain only. The results demonstrate that removal of T cells from donor cells, as well as exclusion of a HVG reaction, make it possible to transplant bone marrow between allogeneic individuals.

Animals↗
PubMed1975

Fc-receptors, Ia-antigens, and immunoglobulin on normal and activated mouse T lymphocytes.

Using antibody coated bovine erythrocytes we were unable to demonstrate Fc-receptors on either thymus cells or T cells prepared from lymph node cell suspensions by anti-Ig column filtration. However, if parental thymus or lymph node T cells were transferred to X-irradiated F1 hybrids, activated donor T cells recovered from the recipient's spleen (ATC-spleen) were shown to express Fc-receptors. Fc-receptors were also demonstrable on ATC-spleen prepared between strain combinations differing at the M-locus. In marked contrast, Fc-receptors were not detected on ATC recovered from thoracic duct lymph (T.TDL). This applied to (a) H-2-activated T.TDL derived from normal thymus cells, (b) H-2-activated T.TDL derived from thymus cells depleted of B cells, and (c) M-locus-activated T.TDL. Of these three populations, surface Ig (of B cell origin) was detected on a large proportion of the first but not on the second and third populations. Thus, the failure to detect Fc-receptors on any of these populations could not be attributed to blocking by adsorbed surface Ig. In addition, various T-cell populations were examined by a microcytotoxicity assay for the presence of cell surface Ia-antigens. 5--10% of the thymus cells, 20--30% of cortisone-resistant thymus cells, 60--70% of lymph node cells, and 60--80% of ATC-spleen and T.TDL showed Ia.

Animals↗
PubMed1975

Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras.

T-B collaboration has been studied in a secondary response to sheep erythrocytes using either syngeneic or allogeneic T- and B-cell combinations. T cells prepared from tetraparental bone marrow chimeras (TBMC), carrying H-2 determinants of one parental strain only, cooperated with syngeneic, as well as with allogeneic B cells carrying the alloantigens to which the T cells had been tolerized in the chimeric environment. When TBMC-derived cells of a single H-2 specificity were transferred with a mixture of TBMC-derived B cells of both H-2 types of the parental strains, no preference for syngeneic cooperation was found. The data therefore suggest that the presence of differing H-2-complex determinants on the allogeneic T- and B-cell populations of the two different strain combinations tested do not interfere with T-B collaboration when the cell populations studied are mutually tolerant.

Animals↗
PubMed1975

Association of immunity and tolerance to host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain.

Semiallogenetic radiation chimeras were prepared by injecting heavily irradiated F1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 times 10-7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100% of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemmaglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes. No evidence could be found that unresponsiveness in this situation was due to blocking serum factors or suppressor T cells. It is argued that the results support the concept that lymphocytes responsive in mixed leukocyte culture have a different specificity to those exerting cell-mediated lympholysis.

Animals↗