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B Kindred

Publications and source records attributed to B Kindred.

At least 37 records · Page 2Linked to original sources

In vivo responses of alloreactive lymphocytes stimulated in vitro. Skin graft rejection mediated by MLR-Primed lymphocytes.

Mouse lymphocytes that have been primed in vitro against alloantigens show a specific increase in cells reactive to the priming antigens in mixed lymphocyte response (MLR) and include cells that are specifically cytotoxic in vitro. The primed population also contains cells capable of causing rejection of skin grafts when injected into nude mice. Functional enrichment of cells capable of rejecting skin grafts bearing specific alloantigens and depletion of cells capable of rejecting a third-party graft have been shown. Priming the cells a second time in vitro may result in a moderate enrichment of cells capable of rejecting the specific graft and depletion of cells reactive to third-party skin compared with once-primed cells. These findings support the prediction that the MLR is an in vitro model of allograft responses in vivo.

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In vivo responses of alloreactive lymphocytes stimulated in vitro. Helper-cell activity of MLR-primed lymphocytes.

Populations of mouse lymphocytes enriched in specific alloreactive cells by priming in a mixed lymphocyte response (MLR) include cells which, when injected into congenic nude mice, enable them to make alloantibody after immunization. Helper cells for the priming H-2 alloantigens (H-2b or H-2k) were enriched relative to helper cells for the other H-2 type. Furthermore, the alloantibody responses of nude mice reconstituted with lymphocytes primed twice in vitro were virtually monospecific for the priming alloantigens. These studies suggest that lymphocytes that proliferate in MLR include lymphocytes capable of giving specific help for H-2 antigens in vivo. Nude mice reconstituted with MLR-primed lymphocytes made less antibody to bacteriophage T4 and phix than mice reconstituted with unprimed cells, and fewer mice responded. Priming of cells a second time in MLR further depleted the population of phage helper cells. Similar results were sometimes, but not always, obtained when testing reconstituted nude mice for their ability to make anti-sheep erythrocyte (SRBC) responses. These results suggest that lymphocytes primed against H-2b or H-2k alloantigens do not have specificity for antigens of T4 or phix. These alloreactive cells may also lack specificity for SRBC. However, the results do not allow a definitive conclusion to be drawn.

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Specific unresponsiveness in nude mice given antigen before T cells.

Nude mice given antigen before being given congenic T cells are specifically tolerant to that antigen and recovery of the ability to respond takes at least 2 weeks. If, after giving antigen, spleen cells are transferred to irradiated congenic recipients together with normal congenic thymocytes, the recipients usually remain unresponsive. Treatment of the spleen cells with supernatant from lysed cells renders them responsive in transfer. Spleen cells from unresponsive mice do not suppress normal spleen cells in transfer and the unresponsiveness is not broken by allogeneic cells. It is therefore probable that this is a case of reversible blocking of the B cell receptors and that T cells are not involved.

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The failure of allogeneic cells to maintain an immune response in nude mice.

Nude mice that have been injected with allogeneic thymus cells and sheep erythrocytes respond for a short time and are then unable to respond to subsequent injections of sheep erythrocytes, even if given with allogeneic thymus cells from the same or a different strain. However, they can respond to a different antigen or to the original antigen if given with congenic thymus cells. B cells from such animals are able to respond if transferred together with congenic thymocytes to irradiated hosts. It is suggested that allogeneic T cells are able to cooperate with B cells to initiate an immune response but that a further step is necessary to maintain the response, and for this congenic T cells are necessary.

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Activity of host-derived T cells which differentiate in nude mice grafted with co-isogenic or allogeneic thymuses.

If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used.

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Differentiation of T-cell precursors in nude mice demonstrated by immunofluorescence of T-cell membrane markers.

When the thymus from an AKR mouse (TL(-), theta-AKR) is grafted to a BALB/c-nu/nu mouse (TL2, theta-C3H), the grafted thymus is rapidly repopulated by host lymphocytes, i.e., lymphocytes having the TL2 and theta-C3H T-lymphocyte membrane antigen markers. theta-C3H lymphocytes also appear rapidly in the spleen and lymph nodes. After a few weeks, BALB/c nude mice grafted with AKR thymus and normal BALB/c mice could not be distinguished on the basis of the number of TL-positive thymocytes or theta-C3H-positive lymphocytes in thymus, spleen, or lymph nodes. These experiments give a definitive proof of the existence of precursor cells for the T compartment of the lymphoid system in the nude mouse. They strongly suggest the involvement of host-derived T cells in the recovery of some T-cell functions by nude mice grafted with allogeneic thymuses.

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