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D Collavo

Publications and source records attributed to D Collavo.

At least 19 recordsLinked to original sources
PubMed1992

Antitumour efficacy of lymphokine-activated killer cells loaded with ricin against experimentally induced lung metastases.

Adoptive transfer of tumour-specific T lymphocytes loaded with ricin into tumour-bearing mice exerts a transient therapeutic effect against locally induced tumours [Cerundolo et al. (1987) Br J Cancer 55: 413]. As transferred cells preferentially locate in the lung, we studied the therapeutic effect of ricin-loaded, lymphokine-activated killer (LAK) cells on lung metastases induced by M4 or B16-F1 (F1) tumour cell injection. In vitro studies demonstrated that ricin-treated LAK cells were about 100-fold more efficient than untreated LAK cells in inhibiting growth of the ricin-sensitive M4 tumour cell line. This effect was most likely due to the released ricin, as treated and untreated LAK cells inhibited the relatively toxin-resistant F1 cell line to the same extent. Ricin treatment did not alter the tissue distribution of intravenously (i.v.) injected LAK cells, which selectively localized in the lung early after inoculation, whether or not metastases were present. Adoptive transfer experiments showed that ricin-treated LAK cells were significantly more efficient than untreated LAK cells in inhibiting M4- but not F1-induced lung metastases. These results indicate that LAK cells are able to deliver a therapeutic concentration of antineoplastic compounds directly to the lung.

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PubMed1992

Role of adhesion molecules in the immune reaction to M-MSV-induced tumors.

We have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs.

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PubMed1992

The in vivo role of leukocyte function-associated antigen-1 in cytotoxic cell activity against tumors induced by Moloney-murine sarcoma/leukemia retroviral complex.

The in vivo role of LFA-1 molecule in the immune reaction to a murine retrovirus-induced tumor was investigated. Local and systemic treatment with high doses of anti-LFA-1 monoclonal antibody led to tumor progression by blocking CTL interaction with tumor cells without interfering with CTL generation and localization in the tumor mass.

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PubMed1991

Moloney murine leukemia virus tolerance in anti-CD4 monoclonal antibody-treated adult mice.

Adult mice injected with Moloney murine leukemia virus (M-MuLV) 1 day after a short term treatment with anti-CD4 mAb developed T cell lymphomas, or sarcomas when rechallenged with Moloney murine sarcoma virus (M-MSV). Neoplastic development was correlated with virus spread, as thymic and peripheral T and B lymphocytes promptly expressed M-MuLV-induced Ag after virus introduction; no virus-specific CTL generation was detected in MLTC. This failure, which was selective for M-MuLV-induced Ag, persisted throughout the life span of the mice, and was not sustained by suppressor cell activity. The frequencies of splenic virus-specific CTL precursor varied in relation to time after virus injection; in the first postinjection month, frequencies were similar to those in nonimmune control mice, while at 4 mo post-virus exposure, they showed a striking reduction. These findings indicate that a transient functional impairment of CD4+ cells at the time of retrovirus injection provided the appropriate milieu for tolerance induction in both the peripheral mature and intrathymic T cell compartments.

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PubMed1991

An improved method for the detection of DNA fragmentation.

An application of the Southern blot technique is described which permits the detection of DNA fragmentation due to cell death by apoptosis. DNA fragments were isolated from cell suspensions and tissues, separated on agarose gel, transferred by Southern blot and hybridized with a radiolabeled total cellular DNA probe. The application of this procedure to thymus cell samples, revealed the distinct ladder pattern of DNA fragments in multiples of about 180-200 base pairs, a characteristic feature of DNA fragmentation. In comparison to conventional DNA visualization with ethidium bromide staining, the radiolabeled probe improved the detection of DNA fragments at least eight-fold. This method detects low levels of DNA fragments, as well as physiological tissue DNA fragmentation, while avoiding cell damage due to DNA radiolabeling.

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PubMed1979

Lack of T-cell mediated cytotoxicity in M-MSV system depending on H-2 haplotypes.

The H-2 restriction phenomenon was evaluated with regard to the immune response to Moloney sarcoma virus (M-MSV)-induced tumours in the mouse. Using an in vitro 51Cr release assay the lytic activity of lymphocytes from M-MSV immune strains of mice, including several H-2 recombinant strains, was determined on leukaemic cell lines originally induced in mice of different strains by neonatal infection with Moloney leukaemia virus. In analogy with other experimental models, it was observed that a compatibility between effector and target cells at the K and/or D regions is generally necessary and sufficient to obtain the cytotoxic effect. However, for the H-2d and H-2b haplotypes, identity at the K or D region respectively was not sufficient for lysis to occur. Attempts to demonstrate that this lack of activity might be associated with the absence of H-2 linked Ir responder genes, were not successful.

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PubMed1978

Colony formation of cytolytic T cells in semisolid medium.

Addition of supernatant from concanavalin A-stimulated spleen cells to in vitro primed cytolytic T lymphocytes in semisolid medium stimulated the growth of colonies of cytolytic lymphocytes. Optimal results were obtained using a peritoneal adherent cell underlayer where a 10% plating efficiency (greater than or equal to 4 cells per colony) was achieved when between 5000 and 100 000 cells were plated per dish. Individual colonies were harvested and tested in a short term (5h) 51Cr release microassay, employing 200 target cells. The frequency of lytic colonies varied from 46--67%. The observed lytic activities were specific for the relevant allogeneic target cells.

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PubMed1978

Proliferative response of H-2 incompatible leukocytes to an Abelson virus-induced lymphoma cell line apparently not expressing Ia-antigens.

The proliferative response of normal lymph node cells from different mouse strains to an Abelson virus-induced leukemic cell line (MLVA) in mixed leukocyte culture (MLC) has been investigated. MLVA leukemic cells do stimulate a specific response and the stimulating determinants are controlled, most likely, by genes in the K-end of the H--2 complex. However, using two different anti-Ia sera and different assay systems, we were unable to detect the expression of Ia-antigens on MLVA. In addition, an alloantiserum raised against MLVA, and absorbed with P815, a nonstimulating mastocytoma cell line, showed no residual activity against MLVA cells.

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PubMed1978

Secondary in vitro generation of cytolytic T-lymphocytes (CTL's) in the murine sarcoma virus system. Virus-specific CTL induction across the H-2 barrier.

Following in vitro stimulation of murine sarcoma virus Moloney isolate (M-MuSV)-immune spleen cells with syngeneic antigenically related Moloney leukemia cells, highly efficient cytotoxic T-lymphocytes (CTL's) were generated. The cytotoxic effect was directed only against H-2-compatible target cells bearing M-MuSV tumor-associated antigens (TAA). However, in a cold target competition assay a weak but detectable capacity to block CTL activity was also obtained when allogeneic Moloney leukemia cells were added. Moreover, when M-MuSV-immune spleen cells from mice inoculated with virus 14 days previously were stimulated by allogeneic Moloney leukemia cells, a strong cytotoxic effect toward syngeneic and allogeneic tumor cells bearing M-MuSV TAA was elicited.

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PubMed1977

Genetics of murine sarcoma virus (MSV)--induced tumors in AKR mice: Evidence that late progressing and early regressing tumors are controlled by different gents.

The genetics of late appearing MSV tumors showing a progressive growth pattern in AKR mice was investigated. The late MSV tumor response in F1 hybrids depended on the genetic background of the non-AKR parent. Within the 4-month observation period following virus injection, (CBA X AKR) F1, (DBA/2 X AKR)F1, and (NIH X AKR)F1 developed progressing MSV tumors, which exhibited latency and growth behavior comparable to that seen in AKR mice, (BALB X AKR)F1, (B6 X AKR)F1, and (B10br x akr)f1 mice did not show any late MSV tumors. In contrast to early regressing M-MSV tumors, whose development is independent of Fv-1 genotype, late MSV tumor progression is largely a function of this gene, since all late tumors which appeared in (B10BR x AKR) x AKR were observed in Fv-1n homozygous mice, H-2k halotype is a further factor in the occurrence of late MSV tumors, at least in (B6 x AKR) x AKR mice. In crosses of AKR with Fv-1 compatible mice, tumor appearance was strongly associated with inheritance of AKR-Mulv, and MSV recovered from late tumors of first back-cross animals appeared to be a new pseudotype with the endogenous AKR-MuLV. It is suggested that the host genetic control in both early and late MSV tumors is exerted mainly on the helper component of the leukemia-sarcoma complex.

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PubMed1977

Inhibitory effect of YC8 leukaemia cell line on in vitro lymphocyte reactivity.

Mitomycin-treated transplantable Moloney virus-induced lymphatic leukaemia cells (YC8) not only failed to stimulate normal allogeneic lymphocytes in one-way mixed leucocyte culture (MLC) but also exerted a strong inhibitory effect on the proliferative response of normal lymphocytes, in MLC and after stimulation by mitogens. Potentially inhibitory factors which could be released in the culture fluids by the YC8 cells were not found, but a YC8-derived adherent cell subpopulation was identified as being responsible for the in vitro suppression.

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PubMed1977

In vitro secondary MLR. I. Kinetics of proliferation and specificity of in vitro primed responder cells.

We have examined the kinetics and specificity of secondary in vitro mixed lymphocyte reactions (MLR). With limited numbers of primed responder cells (PRC) in the presence of "excess antigen" it was possible to obtain proliferative responses that were proportional to the number of PRC initially placed in culture. The responding cells, after an initial lag period, seem to grow exponentially until day 3 of culture. The responses of PRC (with the strain combinations and culture conditions described in this report) seemed to be directed toward stimulator cell determinants whose expression was determined by genes in the I region of the MHC. In one case, the relevant incompatibilities could be further restricted to the I-A region. Although PRC responded best to stimulator cells sharing the I region with the priming stimulator cell, apparent cross-reactivity could be observed by restimulating PRC with stimulator cells that did not carry the MHC haplotype of the priming stimulator cell. The rate of proliferation (measured as 3H-thymidine incorporation) in these apparent cross-reactions was reproducible and comparable to the rate observed in response to the priming stimulator cell. It was possible, therefore, to estimate the proportion of PRC that reacted in the presence of third party stimulator cells compared to the response of these PRC to the priming stimulator cells. We have estimated that the response of A (B6) PRC against H-2d and H-2s haplotype stimulator cells is about half of the response of these PRC to H-2b, the priming stimulator cell.

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PubMed1976

Generation of cytotoxic cells in absence of blastogenesis by mouse leukemic cells in mixed cultures.

Primary virus-induced murine leukemias and transplantable leukemic cell lines, originally induced by virus, chemical or physical agents, failed to stimulate normal spleen cells differing at the H-2 complex or at Mls locus in the one-way mixed leukocyte culture. Lack of stimulation seems at least partially due to a nonspecific inhibitory effect since in a "three-party" culture system the leukemic cells interfered with the mixed leukocyte reaction (MLR) of normal allogeneic cells. Characterization of the leukemic cell populations used, according to their T or B cell origin, disclosed that in most cases T cell markers were present. Also, no Ia antigens were detected on leukemic cells. Furthermore, using a 51Cr release assay, leukemic cells could sensitize allogeneic normal lymphocytes to kill specifically normal as well as leukemic targets, even when no MLR was detected in parallel cultures.

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