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Biomedical subjects

P Liacopoulos

Publications and source records attributed to P Liacopoulos.

88 records · Page 5Linked to original sources
PubMedDate not supplied

Enhancement of Lewis lung carcinoma growth by sera or spleen cells from tumour-bearing mice.

Lewis lung carcinoma(3LL) cells grafted in syngeneic adult C57BL/6 mice produced local tumours associated with lung metastasis in 78% of recipients. Adult thymectomized, lethally irradiated, bone marrow cell-reconstituted animals (B mice) were more resistant since this tumour grew in only 46% of recipients and especially the weight of lung metastasis was almost 8 times less than in normal animals. Sera from tumour-bearing mice transferred into B mice enhanced tumour incidence and weight of metastasis to the level observed in normal mice. In vitro cultured 3LL cells displayed an intense mitogenic activity as measured by 3H-thymidine incorporation. Addition into these cultures of serum from tumour-bearing animals did not alter this activity. Addition of normal spleen cells in a ratio 40/1 reduced this mitogenic activity to a half or a third. Spleen cells from tumour-bearing mice, either normal or serum-enhanced B mice, mixed in vitro with 3LL cells, produced a 4-fold increase of mitogenic activity of the latter. These results indicate that the lymphoid system may contribute to the growth and spreading of 3LL tumours.

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PubMedDate not supplied

Modulation of helper T-cell activity by macrophage products.

Mouse spleen cells cultured with muramyl dipeptide (MDP) release factors (SMF, or splenic macrophage factors) which enhance the in vitro plaque-forming cell (PFC) response to the T-dependent antigen SRBC (sheep red blood cells). The present study substantiates previous results and shows that T cells were the target cells of such conditioned medium. We investigated which T-cell subpopulations had their activities modified by these factors. In the presence of SMF, T cells educated in vivo elicited enhanced PFC responses to both specific educating antigen and an unrelated antigen (during a bystander response). This could indicate that SMF potentiates Th2-cell activity. Moreover, in vivo matured but unprimed thymocytes, which are unable to cooperate with virgin B cells in an in vitro T-dependent response, are able to do so when SMF is added in cooperative cultures. It is concluded that MDP-conditioned medium allows the maturation/differentiation of a subset of T cells to the point where they can be stimulated by the antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

[Heterogeneity of antibodies produced by individual cells].

Recent experimental findings indicate that individual B cells can produce simultaneously heterogeneous Ig molecules. Three orders of heterogeneity have been described. (1) In two published cases of human myeloma, individual malignant cells produced Igkappa and Iglambda (case Im) or IgMlambda and IgGkappa (case Br). (2) Immunofluorescence studies repeatedly showed that normal B cells may bear surface Ig of two different classes or cytoplasmic Ig of one class and surface Ig of another class. However, simultaneous production of two different CH chains by immunized B cells or myeloma cells appeared to be rather rare (1-3%). (3) Immunization of mice with two different antigens regularly results in the appearance of cells (1-3%) simultaneously reacting with both antigens. Specific inhibition of the one activity does not interfere with the other. Furthermore, bispecific cells cultured individually generate daughter cells, each producing antibody of only the one or the other specificity. It can be inferred from these findings that early B lymphocytes are pluripotential and that differentiation involves a process of phenotypical restriction directing the cell (plasma cell) to produce high quantities of one type of Ig molecule.

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PubMedDate not supplied

Induction of tolerance in adult guinea-pigs by two antigen dosage levels and by antigenic competition.

The effect of prior injection of increasing doses of dinitrophenylated bovine serum albumin (DNP-BSA) mixed in Freund's complete (FCA) or incomplete (IFA) adjuvants on the antibody response to a subsequent challenge with an optimal immunizing dose of DNP-BSA in FCA has been examined and compared with the effect of competition with the unrelated antigen bovine gamma-globulin (BGG). An unresponsive state was induced by pretreatments with either a minimal dose of antigen, a large antigen excess or a competitive mixture in FCA. The specificity of this unresponsiveness was ascertained by the normal response of pretreated animals to the unrelated antigen arsanilic-human albumin (ARS-HSA). Prior injection of either a minimal dose (0,2 mug), an antigen excess (20 mg) of DNP-BSA or an optimal dose (20 mug) of DNP-BSA mixed with an excess of BGG, incorporated in IFA, also induced a specific tolerance to DNP-BSA. The former treatment induced a low zone tolerance whereas both later treatments induced a high zone tolerance.

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PubMedDate not supplied

Evidence for multipotentiality of antibody synthesizing cells.

Immunization of mice with two unrelated antigens or antigenic determinants regularly results in the appearance of hemolytic plaque forming cells (PFC) of each specificity and of some PFC (1-4%) reacting to both determinants. Micromanipulation of individual double PFC appearing after immunization with trinitrophenyl conjugated sheep erythrocytes (TNP-SRBC) into media containing indicator erythrocytes (native SRBC and TNP-horse RBC) and a soluble specific inhibitor (TNP-BSA or soluble SRBC antigen), showed that the specific inhibitor suppressed the lysis of the corresponding indicator but did not interfered with the lysis of the unrelated indicator. Persistance of one specific activity in spite of complete inhibition of the other indicated that these double PFC synthesize two different antibody molecules. The destiny of double cells was studied in individual cell cultures by micromanipulating them into wells containing heavily irradiated normal mouse spleen cells and both determinants (TNP-SRBC). Those double cells which divided they generated in 24 hours monospecific daughter PFC (either anti-TNP or anti-native SRBC). Individually cultured monospecific PFC from mice immunized with one antigen (native SRBC) generated daughter PFC of the same specificity. By contrast, monospecific PFC from mice immunized with TNP-SRBC generated PFC of either the same specificity of (more frequently) of the one the other specificity. Thus, immunization with substituted erythrocytes resulted in the development of three clonotypes: two clones each composed only of cells of either specificity (amphispecific clonotype). For the maintenance of this amphispecific clone, continuous presence in the culture media of both antigenic determinants was necessary. Removal of the one for 48 hours (but not for 24 hours) abolished the generation of daughter cells of the same specificity.

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