The Morphologic Responses of the Lymphoid System to Homografts. II. The Effects of Antimetabolites

André, Janine A.; Schwartz, Robert S.; Mitus, W. J.; Dameshek, William

doi:10.1182/blood.v19.3.334.334

Cited by 45 publications

(3 citation statements)

References 9 publications

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“…If treatment could have been prolonged, an increase in per cent of labeled lymphocytes might have been found. Morphological alterations of lymphoid tissues during 6-mercaptopurine treatment have previously been found to be variable even in rabbits (15), the animal in which immune reactivity is most susceptible to 6-mercaptopurine (2). Further, it has been suggested that the effect of 6-mercaptopurine on the manifestations of immunological reactions may be a direct antiinflammatory action (16), and that its value in human clinical situations, or that of azathioprine, may be in its ability to establish tolerance (1,17) rather than by simply stopping antibody production.…”

Section: Discussionmentioning

confidence: 99%

Resistance of Long-Lived Lymphocytes and Plasma Cells in Rat Lymph Nodes to Treatment With Prednisone, Cyclophosphamide, 6-Mercaptopurine, and Actinomycin D

Miller

Cole

1967

The Journal of Experimental Medicine

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The cells of the popliteal lymph nodes of rats were labeled for 4 days after a secondary immunological stimulus. 31 days after the last dose of tritiated thymidine, groups of rats were started on courses of daily, intraperitoneal injections of prednisone, cyclophosphamide, 6-mercaptopurine, or actinomycin D. The initially low doses of these agents were doubled in successive weeks until either lymphoid hypoplasia or death occurred. Rats from each group were killed weekly, and the percentages of persisting, labeled small lymphocytes in the popliteal nodes were determined. Sections of these nodes were examined for persisting, labeled plasma cells. The per cent of lymphocytes labeled increased while the total number of lymphocytes decreased during treatment with prednisone and cyclophosphamide. Prednisone decreased the numbers of long-lived plasma cells, but these cells were preferentially resistant to cyclophosphamide. Neither 6-mercaptopurine nor actinomycin D had an appreciable effect on lymphoid tissues histologically nor on the proportions of labeled, long-lived lymphocytes and plasma cells before causing the deaths of the rats receiving them. These results indicate that long-lived lymphocytes and plasma cells survive treatment with the immunolytic drugs studied, and that long-lived lymphocytes are specifically resistant to prednisone and cyclophosphamide. We believe these results have an application to the attempts to find drugs useful in the treatment of immunologic rejections of organ transplants, and for therapy of autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Resistance of Long-Lived Lymphocytes and Plasma Cells in Rat Lymph Nodes to Treatment With Prednisone, Cyclophosphamide, 6-Mercaptopurine, and Actinomycin D

Miller

Cole

1967

The Journal of Experimental Medicine

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“…The failure of azathioprine to interfere with passive immunization suggests that it may not be active against immunologically committed cells. It did, however, interfere with the development of immunity during a primary Listeri~ infection (3), suggesting that its immunosuppressive effect may be limited to a step in the inductive phase of the immune response, as has been suggested in the case of a closely allied drug, 6-mercaptopurine (14).…”

Section: Effect Of Treatment Of Donors With Single Doses O/drugs a Damentioning

confidence: 99%

The Effect of Cytotoxic Agents on the Passive Transfer of Cell-Mediated Immunity

Tripathy

Mackaness

1969

The Journal of Experimental Medicine

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A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation. Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine. The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.

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“…This test for capillary fragility is also positive in other types of vasctilitis. 3. The correct answer is B, 4 months.…”

mentioning

confidence: 97%

Indicatioins for Thalidomide Therapy for Leprosy

Klüken

1974

Int J Dermatology

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The Morphologic Responses of the Lymphoid System to Homografts. II. The Effects of Antimetabolites

Cited by 45 publications

References 9 publications

Resistance of Long-Lived Lymphocytes and Plasma Cells in Rat Lymph Nodes to Treatment With Prednisone, Cyclophosphamide, 6-Mercaptopurine, and Actinomycin D

Resistance of Long-Lived Lymphocytes and Plasma Cells in Rat Lymph Nodes to Treatment With Prednisone, Cyclophosphamide, 6-Mercaptopurine, and Actinomycin D

The Effect of Cytotoxic Agents on the Passive Transfer of Cell-Mediated Immunity

Indicatioins for Thalidomide Therapy for Leprosy

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