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C D Pasqualini

Publications and source records attributed to C D Pasqualini.

At least 55 records · Page 3Linked to original sources

Early increase in graft-versus-host reactivity during pregnancy in the mouse.

Alloreactive T levels of para-aortic lymph nodes (PALN) and spleen were determined on different days of pregnancy in BALB/c females by local and systemic graft-versus-host (GvH) assays. A significant increase in GvH reactivity was registered early in both allogeneic and syngeneic matings, operating not only towards paternal but also towards third party strains. Immunoregulatory mechanisms in PALN also involved the appearance of progressive suppression during the first days of pregnancy. The possible role of non-specific early increases in T alloreactivity in triggering suppressor mechanisms and the nature of the immunogens responsible for the alterations in GvH reactivity are discussed.

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Maternal immunoregulation: interrelationship between alloreactive and anti-self plus conventional antigen T sets of cells.

In a previous paper we reported early immunoregulatory mechanisms involving not only the appearance of progressive suppression but also significant increases in alloreactive T levels in paraaortic lymph nodes (PALN) and spleen, not only in allogeneic but also in syngeneic pregnancies. Taking into account the hypothesis of the superposition of the alloreactive and the anti-self plus conventional antigens T sets of cells, we investigated whether immunization with conventional antigens was able to alter alloreactive T levels. Weekly i.p. doses of rabbit red bloods cells (RRBC) in BALB/c mice resulted in a dose-dependent increase in spleen alloreactivity as determined by graft-versus-host (GvH) assays in strain combinations differing at H-2 level but not in those sharing the same H-2 with BALB/c. The increases could be significantly decreased by an anti-idiotype anti-RRBC serum. Pretreatment with i.p. weekly doses of sheep red blood cells (SRBC) before mating was able to induce dose-dependent fetal damage when the parents differed at the H-2 level. SRBC immunization in one of the uterine horns induced increases in PALN weight which were much higher in progesterone-pseudopregnant than in virgin mice; T alloreactivity was significantly increased in the draining PALN only in pseudopregnant females. These results favour the postulation of the superposition between the alloreactive and the anti-self plus conventional antigens T sets of cells and suggest a possible role for conventional fetal antigens (non H-2) in triggering immunoregulatory mechanisms operating in pregnancy.

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Immunochemical behaviour of a tumour-associated antigen obtained from an AKR mouse lymphoma.

A soluble tumour-associated antigen was prepared by homogenizing AKR lymphoma cells (L15) followed by treatment with acetone and glycine-HCl buffer pH 3. It was analyzed by immunoelectrophoresis, rocket electrophoresis in the presence of Concanavalin A and SDS-PAGE. It showed rapid electrophoretic mobility, and the major component had an estimated molecular weight of 70,000 daltons. The molecular composition of the antigen included a glycoprotein. Specific antibodies against this antigen were demonstrated in BALB/c mice in which the AKR lymphoma was conditioned to grow by introducing the L15 cells into a subcutaneously implanted glass cylinder. In this model antibodies were found in both tumour-bearing (progressor) and tumour-rejecting (regressor) animals. In vivo experiments showed that pretreatment of BALB/c mice with L15 acellular extracts, 10 days before tumour challenge, led to a significant increase in allogeneic tumour growth. A rabbit anti-tumour extract serum was prepared and was rendered tumour -specific by exhaustive absorption with normal AKR serum and tissues. It shared the same epitopic specificity with tumour progressor or regressor mouse sera since indirect immunofluorescence using L15 cells could be reciprocally inhibited.

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"Concomitant immunity" in murine tumours of non-detectable immunogenicity.

Various immunization assays were used to demonstrate the lack of immunogenicity of three BALB/c tumours of spontaneous origin and of a fourth one resulting from foreign body tumorigenesis. All four tumours inhibited the growth of a second implant of the same tumour into the contralateral flank. In our tumour models "concomitant immunity" (1) was not mediated by macrophage or T-cell dependent immune reactions: both thymectomized BALB/c and nude mice (treated or untreated with silica) gave the same results as intact mice; (2) showed some degree of non-specificity, inhibiting the growth of a different tumour in 3/4 cases; though, the existence of a specific component could not be discarded; (3) was proportional to the volume of the primary tumour at the time of the second challenge; (4) was dependent on actively growing primary tumour, not being obtained with progressively increasing daily inocula of irradiated tumour cells; (5) was detectable in an actively growing secondary tumour; recurrent growth after partial surgical excision was inhibited and (6) involved cytostasis of the secondary tumour: a syngeneic graft of the overlying skin led to tumour growth while histological studies revealed the presence of viable tumour cells. It is postulated that "concomitant immunity" or resistance can be generated without the active participation of the immune system and that tumour-related factors are, in certain cases, responsible for blocking the growth of secondary tumours.

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Macrophages and tumor growth. II. Cell kinetics at the site of allogeneic tumor growth.

The sponge matrix allograft model made possible the growth of an AKR lymphoma in a certain percentage of BALB/c mice making progressors (tumor-bearing) and regressors (tumor-rejecting) simultaneously available. Mice bearing either an AKR kidney allograft or a sponge alone were used as controls. The cell population infiltrating the sponge was evaluated 2, 5, 10, 15, and 21 days after subcutaneous implantation. It consisted of macrophages, lymphocytes, and neutrophils. There was no difference between groups on Day 2 and Day 5. From Day 10 onwards, tumor growth was evident with a clear cut separation between progressors and regressors. The latter behaved like the two control groups except for a significant increase in lymphocytes on Day 21. The progressors showed a striking increase in total cell count from Day 10 onwards. Macrophages were the major population with a maximum value of 201 X 10(6) as compared to 8 X 10(6) in the regressors; their phagocytic and lysosomal activity remained similar in all groups. The lymphocytes showed no variation in absolute numbers but, because of the high cell count in progressors, their ratio to macrophages reached 1:50 on Day 10, making up only 2% of the cell population. Neutrophils were significantly increased in progressors as compared with the other groups. It can be concluded that in the presence of a foreign body reaction a marked influx of macrophages accompanies allogeneic tumor growth.

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Antibodies against a tumour-associated antigen in an AKR lymphoma conditioned to grow in BALB/c mice.

An experimental model was used in which AKR lymphoma cells (L15) were conditioned to grow in BALB/c mice leading to tumour-bearing (progressor) and tumour-rejecting (regressor) animals. The behaviour of antibodies present in the sera of these animals was studied using as antigen L15 cells or a soluble tumour-associated antigen TEs. Both sera showed similar IIF and haemagglutinating activity. However differences were observed for the complement cytotoxicity assay. Regressor serum as well as a rabbit anti-tumour-associated antigen serum were strongly cytotoxic for the AKR lymphoma cells while progressor serum showed markedly lower activity. Specific antibodies against the tumour-associated antigen were purified. In both sera they were located mainly in IgG1 but also in IgG2. The purified antibodies agglutinated specifically sensitized sheep erythrocytes and reacted by indirect immunofluorescence with L15 cells but not with AKR thymocytes. It is suggested that two qualitatively different humoral immune responses are involved in the mechanisms leading to tumour enhancement or rejection.

AKR murine leukemia virus↗

Antibodies presumably cross-reacting with mouse retrovirus type B and C in the sera of both leukemia-lymphoma and mammary cancer patients.

In the mouse, retrovirus B and C are causal agents of mammary cancer and leukemia, respectively. In previous work it was demonstrated that sera of leukemia-lymphoma patients possess antibodies which react with antigenic determinants of Type C virus present on AKR-lymphoma and AKR-thymus targets. The object of this paper was to determine whether these antibodies also reacted with Type B viral antigens present on a virus-induced BALB-mammary carcinoma; at the same time a comparative study was carried out with sera of breast cancer patients. A total of 325 sera were obtained from 277 leukemia-lymphoma cases under protocol treatment: 232 acute lymphoid leukemia, 23 acute myeloid leukemia, 15 chronic myeloid leukemia and 55 Hodgkin lymphoma sera. A total of 240 sera were obtained from breast cancer patients at the time of diagnosis and 196 sera from normal blood donors served as controls. Using indirect immunofluorescence with labeled anti-human IgG and the murine targets, antibodies were encountered in a high percentage of cancer cases and were consistently absent in normal sera. The results confirm the presence of antibodies reacting with murine Type C virus in leukemia-lymphoma cases and indicate the presence of antibodies reacting to both Type B and C retroviruses in the sera of breast cancer patients.

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Immunization against primary, transplanted and spontaneous murine leukaemia using a live Moloney sarcoma virus vaccine.

The purpose of this study was to use an immunization protocol with Moloney sarcoma virus (MSV-M) as active immunogen against exogenous and endogenous leukaemia. The s.c. route was chosen since it offered advantages over the i.m. route: the primary sarcomas were smaller, the regression faster, there were fewer recurrences and there was good persistent immunity. Strong protection was obtained against primary leukaemias induced by Friend leukaemia virus (FLV), Moloney leukaemia virus (MLV), Rauscher leukaemia virus (RLV), Precerutti-Law leukaemia virus (PLLV/T2), and H179A leukaemia virus. It was not possible to protect against leukaemia induced by Gross leukaemia virus (GLV). With transplantable leukaemias the results varied: partial protection was observed against H110 leukaemia (induced with human material) and R14 leukaemia (induced by X-irradiation) whilst no protection was obtained against P277 leukaemia (induced by Moloney leukaemia virus). As for spontaneous leukaemias, immunized BALB/c mice showed an increased incidence over the controls, while in F1 (Swiss x AKR) mice the incidence was similar but the latent period was shorter. Furthermore, in long-term observations the MSV-M-immunized mice showed an increased mortaltiy, which could be related to (1) new phenotypic mixtures between MSV-M and leukaemia viruses; (2) reactivation of MSV-M sarcoma-genesis with age, and (3) genotype susceptibility to MSV-M.

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Normal murine endogenous lymphoid factor(s) inhibiting lymphocyte functions. I. In vivo effect on allogeneic tumor growth.

Murine lymphoid chalones and their in vivo effect was studied. Cytoplasmic extracts were prepared from normal murine spleen lymphocytes. When assayed in vitro, cytoplasmic extracts (CE) were able to inhibit a blastomitogenic phytohemagglutinin (PHA) response of syngeneic and allogeneic normal murine lymphocytes, as well as cell replication of murine lymphoma cells. CE also had an inhibitory effect on human lymphoblastoid cell line division but it had no effect on nonlymphoid cell division. In vivo, CE had an enhancing effect on a murine allogeneic tumor, probably by suppressing the host's immune rejection response.

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Kinetics of the graft versus host reaction during allogeneic tumour enhancement.

An experimental model has been devised which conditions for tumour enhancement, in which an AKR lymphoma (L15) inoculated within a glass cylinder (GC) implanted under the skin of BALB mice leads to the development of an allogenic lymphoma which kills 55% of the animals in an average of 37 days; L 15 implanted s.c. does not grow in BALB mice. In order to compare the T lymphocyte response of BALB mice inoculated with L 15 by the s.c. and the GC route, the capacity of their spleen cells to induce a graft versus host (GvH) reaction was determined in F 1 (BALB X AKR) on day 0, 3, 10, 14 and 31 after tumour challenge. The kinetics of the GvH reaction followed opposite trends: while the s.c. route led to a very gradual increase, the GC route yielded early high values which gradually decreased to minimum in tumour-bearing animals on day 31. On that day, the animals which had rejected the tumour, by either route, yielded high GvH values. The sole inoculation of acellular tumour extracts (AE L 15), without tumour challenge, also led to a high GvH response. The GvH reaction carried out in F1 (BALB X C57B1/Ks) only gave a positive response in the animals inoculated by the GC route, suggesting that minor histo-compatibility antigens are involved in the early response characteristic of this group. It is concluded that allogeneic tumour enhancement in this model, is accompanied by a marked and early stimulation of T cells, contrasting with the late response obtained in animals rejecting the tumour.

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