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D Redelman

Publications and source records attributed to D Redelman.

46 records · Page 3Linked to original sources

In vitro studies of the rabbit immune system. VII. The generation of rabbit anti-mouse cytotoxic T lymphocytes.

Lymphocytes from normal or immunized rabbits generated cell-mediated cytotoxic activity (CML) after culture with mitomycin C-treated mouse stimulator cells for 4--7 days. CML activity was detected in short term (4--6 h) isotope-release assays using 51Cr-labeled tumor cells or mitogen stimulated blast cells as targets. Rabbit CML effectors could distinguish between different mouse strains including congenics differing only at H-2. It was previously shown that rabbit CML precursors and effectors expressed antigens recognized by a specific anti-T cell serum (ATS). The current results demonstrate that T-enriched fractions from nylon wool columns were enriched for CTL precursors and were sufficient to generate CML responses. These data were most consistent with the xenogeneic CML being mediated by rabbit cytotoxic T-lymphocytes (CTL) analogous to murine CTL. Rabbit lymphocytes also produced a strong mixed lymphocyte (MLC) response when tested in microculture with mouse stimulator cells. However, optimal CML and MLC responses did not occur in lymphocytes from the same organ sources or subpopulation. These data implied that CML activity could be generated with little, if any, proliferation necessary.

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In vitro studies of the rabbit immune system. VI. Rabbit anti-mouse cytotoxic T effector cells are inhibited by anti-rabbit T cell serum in the absence of complement.

Xenogeneic rabbit anti-mouse cell-mediated cytotoxic activity could be generated by culturing lymphoid cells from mesenteric lymph nodes (MLN), spleen, or peripheral blood of rabbits primed 2 to 8 weeks earlier with mouse tumor or spleen cells. MLN cells, which provided the best source of activity after being cultured with 5 to 10 X 10(6) mitomycin C-treated mouse spleen cells for 4 to 6 days, produced 30 to 90% specific isotope release after 4 to 7 hr incubation with 15Cr-labeled tumor target cells. Xenogeneic cytotoxic activity was primarily H-2 specific and could not be blocked by immune complexes but was abrogated by treatment with goat anti-rabbit thymocyte serum plus complement (ATS + C) before or after culture. Therefore, the activity appeared to be mediated by cytotoxic T lymphocytes (CTL). Furthermore, ATS without C abrogated cytotoxic activity when included in the CTL assay at concentrations of 5 to 15 microliter/10(7) effector cells. The inhibitory activity of ATS was directed to the rabbit effector population and could be absorbed completely by rabbit thymocytes. Antisera to mouse T cells with comparable cytolytic activity in the presence of C did not inhibit murine allogeneic CTL.

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Requirements for inducing tolerance of hapten-specific delayed hypersensitivity: epitope density.

Tolerance to hapten-specific antibody formation and delayed hypersensitivity was examined in adult rabbits. The azobenzenearsonate (ABA) or sulfonate-specific antibody response to hapten-hemocyanin immunogens was suppressed by deaggregated hapten-rabbit IgG conjugates given 21 and 14 days before challenge. High affinity antibody was preferentially suppressed. Delayed hypersensitivity to ABA-tyrosine was suppressed by deaggregated ABA-rabbit IgG conjugates injected 17 and 10 days before challenge. Conjugates with a high hapten density, ABA15-23-rabbit IgG were effective tolerogens. Conjugates with four to six ABA groups per carrier molecule were very poor tolerogens. Increasing the amount of low substituted conjugate injected did not improve tolerogenicity. It appears that a high epitope density is required for effective induction of tolerance to ABA-specific delayed hypersensitivity in the rabbit.

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In vitro studies of the rabbit immune system. V. Suppressor T cells activated by concanavalin A block the proliferation, not the induction of antierythrocyte plaque-forming cells.

The late B-cell proliferative phase of the in vitro antibody response by rabbit spleen cells is highly susceptible to suppression by activated T cells. The in vitro antisheep erythrocyte plaque-forming cell (PFC) response by spleen cells from normal or primed rabbits can be suppressed by adding concanavalin A (Con A), Con A-prestimulated peripheral blood or spleen lymphocytes, or supernates from Con A-prestimulated peripheral blood lymphocytes. The suppression is not mediated by a direct interaction of Con A with responding cells as shown by the effectiveness of prestimulated cells. Primed spleen cultures remain sensitive to Con A suppression as late as 72 h after initiation, and the addition of Con A after 24-72 h rapidly stops the increase in the number of PFC. T cells are required for Con A addition to be effective but the suppression can be induced at a time when T-helper cells are no longer necessary. Further, the suppressive effect of Con A addition is abrogated by specific antisera to rabbit T cells. We propose that Con A activates suppressor T cells which then exert their effects on proliferating PFC or their immediate precursor B cells. The early inductive or recruitment phase of the response is probably not blocked by suppressor cells. Also, there is an apparent relationship between the number of proliferating B cells and the number of suppressor cells required. Finally, the difficulties in inducing a stimulatory effect by Con A and the prolonged period that Con A addition is suppressive suggests that the rabbit has relatively more and/or longer-lived suppressor cells than the mouse and may be a particularly useful species for studying suppressive phenomena and their mechanisms.

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