Biomedical subjects

F Pericle

Publications and source records attributed to F Pericle.

23 records · Page 2Linked to original sources

PubMed1994

An efficient Th2-type memory follows CD8+ lymphocyte-driven and eosinophil-mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL-4.

A retroviral infection was used to introduce the cDNA coding for mouse IL-4 into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TS/A-pc). Four clones releasing between 5 to 40 U of IL-4 (10(5) cells) in 48 h culture were selected. The secretion of IL-4 does not affect their in vitro growth, whereas their ability to form tumor in vivo inversely correlates with the amount of IL-4 secreted. Although morphologic observation suggested that the rejection of clone D5.40 cells (releasing 40 U of IL-4) depends on eosinophil cytolysis, lymphocyte depletion experiments showed that this required CD8+ lymphocyte guidance. Mice that had rejected D5.40 cells were immune to a subsequent challenge with TS/A-pc. This memory rests on the interaction between noncytotoxic lymphocytes, eosinophils, and IgG1 and IgE anti-TS/A Abs. Comparison of these memory mechanisms with those elicited by IL-2 gene-transduced TS/A cells shows that the kind of cytokine released by the tumor cells determines the type of response. This Th2 memory seems to be more efficient in protecting against a subsequent challenge of TS/A-pc than the Th1-type memory elicited by IL-2 gene-transduced TS/A cells.

Adenocarcinoma↗

PubMed1994

Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12.

Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5-year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also revealed severe toxicities associated with the use of IL-2. IL-12 is a newly described cytokine that has several properties, including the ability to act synergistically with IL-2 in generating lymphokine-activated killer cells (LAK) against known tumor targets. We investigated the role of IL-12 in the generation of peripheral blood mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were activated with IL-12 alone and in combination with IL-2. Whereas IL-12 alone produced only modest enhancement of NK cell cytotoxicity, the combination of IL-2 and IL-12 was most effective in activating NK cell lysis of neuroblastoma cell lines. Further, we showed that large granular lymphocytes were the effector cells involved in target cell lysis. Finally, the CD18 molecule was shown to be critical in the lysis of neuroblastoma cells by activated PBMC.

Antigens, CD↗

PubMed1994

Interleukin-2 prevention of apoptosis in human neutrophils.

Evidence is presented that interleukin (IL)-2 maintains viability of human polymorphonuclear cells (PMN) in culture by preventing these cells from undergoing programmed cell death (PCD) and induces the synthesis of new RNA and protein. Our laboratory has recently discovered that human PMN constitutively express IL-2 beta receptor and more importantly, PMN are able to respond functionally to IL-2 by enhanced growth inhibitory activity against an opportunistic fungal pathogen, Candida albicans. We now report that IL-2 was able to interfere with the PCD process and reduce the number of apoptotic PMN to < 40% in 72-h culture. Freshly isolated PMN usually underwent a time-dependent aging process and > 80% of PMN cultured in medium alone for 72 h showed morphologic features of PCD as depicted by hematoxylin and eosin staining as well as by electron microscopy. During the PCD process, untreated PMN not only exhibited condensed nuclear structure and decrease in cell size, but also displayed DNA fragmentation. DNA fragmentation in PMN was prevented by IL-2. Prevention of PCD by IL-2 was associated with an increase in new RNA and protein synthesis in PMN, which may reflect cytokine induction, such as tumor necrosis factor, as we have recently shown. Thus, our data expands our current understanding of PMN in that they may be an active component of the immune system, with a longer life-span when activated than expected.

Apoptosis↗

PubMed1993

Strategies for cytokine utilisation in tumor therapy.

The state of the art with regard to the employment of various cytokine-based tumor immunotherapy strategies and their mechanisms of action are critically reviewed. As matters now stand, adoptive transfer of LAK cells or tumor infiltrating lymphocytes together with high doses of IL-2 constitutes the only immunologic way to hinder tumor growth in advanced stages of cancer. On the other hand, many experimental data show that the local presence of cytokines, either injected repeatedly at tumor site or released by cytokine-gene engineered tumor cells, arouses immunogenicity in apparently nonimmunogenic spontaneous tumors. By strengthening the notion that most tumors are potentially immunogenic, these findings offer substantial evidence to stress the potential use of cytokines as a component of new tumor vaccines.

Animals↗

PubMed1991

Growth and dissemination of human malignant lymphoblasts in immunosuppressed nu/nu mice.

Athymic nu/nu mice are commonly employed for the heterotransplantation of solid human tumors. Leukemias, however, have consistently proved difficult to transplant and, to enhance their take, recipient nu/nu mice have been variously immunosuppressed. In this study, the natural reactivity against human malignant T lymphoblast (PF382) of splenectomized nu/nu mice (S-nu/nu), nu/nu mice splenectomized and treated with polyinosinic-polycytidylic acid (SIC-nu/nu), and nu/nu mice splenectomized, irradiated and repeatedly injected with antiasialo GM1 antiserum (SIA-nu/nu) has been correlated with the in vivo growth of subcutaneous and intravenous PF382 cell challenges. SIC-nu/nu mice display a marked natural killer (NK) activity, quickly clear 125I-Urd-labelled PF382 cells injected intravenously and do not allow the growth of subcutaneous nor intravenous PF382 cell challenges. S-nu/nu mice display a slightly lower NK activity and slower clearance of 125I-Urd-labelled PF382 cells. Moreover, an intravenous PF382 cell challenge kills 56% of S-nu/nu mice. SIA-nu/nu mice have no NK activity, slowly clear 125I-Urd-labelled PF382 cells and always allow the growth of PF382 cells injected either subcutaneously or intravenously with a consistent pattern. Following the intravenous challenge, PF382 cells first metastasize to liver and kideny, then focal or diffuse infiltrations of the bone marrow and menings become evident. SIA-nu/nu mice thus offer an interesting experimental model for study of the pathogenesis of leukemic infiltration of the meninges, and the exploration of possible therapeutic approaches.

Animals↗