Biomedical subjects
Publications and source records attributed to D F Tucker.
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The immunosuppresive effects of the bisdioxopiperazines ICRF 154 and ICRF 159 on the function of bone marrow-derived lymphocytes (B cells) and thymusderived lymphocytes (T cells) were assessed and compared with those of cyclophosphamide (CPA). Mice given foreign erythrocytes with any of these drugs for 3 or 5 days showed suppressed antibody responses due to the inhibition of thymus-derived cooperating lymphocyte (T-helper cell) priming and inactivation of B cells in the spleen. In contrast, 3 days of drug treatment after the injection of allogeneic tumor cells only partially inhibited T cell-dependent cytotoxicity. Moreover, when irradiated tumor cells were given for 3 days with CPA or ICRF 154, enhancement rather than inhibition of cytotoxicity was the usual response. However, with both types of immunization, no thymus-derived cytotoxic lymphocytes (T killer cells) could be generated after prolonged treatment (6 daily injections) with any of the 3 drugs. Administration of drugs before antigen also resulted in selective drug action, i.e., a relative increase in the proportion of thy-1-positive cells in the spleen. After challenge in vivo or in vitro with erythrocyte antigens, the plaque-forming cell responses of these spleens were raised up to twofold, probably because they had higher T-helper cell activity than untreated controls. Similar pretreatment before immunization with allogeneic tumor cells also led to enhanced T-killer cell activity, but only in ICRF 154- and CPA-treated mice. These observations suggest that under certain conditions, the bisdioxopiperazines and CPA have selective effects on B-cell rather than T-cell function.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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The induction of immunity to progressively growing murine sarcoma virus (MSV) tumours in nude (nu/nu) mice by reconstitution with immune T cells from syngeneic (+/+) donors has been studied. Whole spleen cell preparations served as the source of immune T cells. Transfer of immune, but not of normal, spleen cells resulted in partial or apparently complete regression of primary tumours and a related moderate to considerable extension of survival time. The dose, the time in days between immunization and transfer, as well as timing of the spleen cells in relation to tumour cell challenge, were all factors which influenced the effectiveness of the protective inocula. An unexpected consequence of even the very effective primary immunotherapy regimens, was secondary tumour development after varying tumour-free intervals. This was most frequently manifest as tumour recurrences at the original injection site either on their own or in combination with distant metastases. Such a relatively high frequency of tumour reappearance and metastatic spread contrasts markedly with the rare instances of secondary regrowth in normal immunocompetent mice. The present reconstitution system may therefore provide a new model for studying the inhibitory or stimulatory properties of T cells with respect to tumour regression and dissemination.
In seven separate experiments, nude (nu/nu) mice carrying established murine sarcoma virus (MSV) tumours were reconstituted with syngeneic (+/+) immune splenic T cells. These immune protected mice were randomly divided to provide smaller groups for serial exsanguination. At various time points mice were individually bled and CIC concentration and blocking activity of each individual serum was determined. Control sera were obtained from nu/nu and adult +/+ mice inoculated with tumour cells only, and from nu/nu mice protected with normal +/+ spleen cells. In all the mice studied, CIC and blocking appeared to be mutually independent parameters throughout the MSV tumour course. On the other hand, in immune protected mice considered alone or together with the control groups, CIC and time after tumour cell inoculation, but not tumour size, were significantly correlated. A significant relationship between blocking and tumour size was also established, although this only applied to immune protected mice. However, analysis of the combined data from sequentially bled immune protected mice in relation to different phases of tumour behaviour, did not support the notion that blocking, and more particularly the persistence of CIC, contribute to tumour regrowth and dissemination.