PubMed HealthSearch

Biomedical subjects

M L Howe

Publications and source records attributed to M L Howe.

28 records · Page 2Linked to original sources

Lymphoid cell subpopulations. I. Synergy between lymph node cells and thymocytes in response to alloantigens and mitogens.

Mixtures of isogenic thymocytes (TC) and lymph node cells (LNC) were shown to exhibit synergistic responsiveness to M and H-2 alloantigens in the mixed lymphocyte interaction (MLI). With respect to the kinetics and magnitude of proliferation and effector cell generation, the response occurring in synergizing cultures closely resembled that of optimal numbers of LNC or spleen cells (SC). In addition, the antigen specificity of effector cells generated by synergizing cultures was similar to that of effectors derived from cultures containing optimal numbers of responding SC. LNC-TC mixtures also exhibited synergy in response to the phytomitogens concanavalin A and pokeweed mitogen but not to phytohemagglutinin. Weakly positive synergy was observed in response to bacterial lipopolysaccharide. It is proposed that the phenomenon of synergy is not restricted to cultures containing mixtures of LNC and TC but also occurs in cultures containing optimal numbers of LNC or SC as a result of interactions between subpopulations of lymphocytes contained within these tissues.

Animals

Enumeration of activated thymus-derived lymphocytes by the virus plaque assay.

Lymphocytes activated by antigens or mitogens acquire the capacity to replicate viruses, and the number of activated lymphocytes can be estimated by the virus plaque assay. Concanavalin A and pokeweed mitogen produced 33-fold and 17-fold increases in virus plaqueforming cells (V-PFC), respectively, above background, while lipopolysaccharide produced only a 2- to 3-fold increase. T (thymus-derived lymphocyte)-depleted lymphocyte populations, derived from anti-theta-treated or nude (arthymic) mouse spleens, failed to produce V-PFC after culture with concanavalin A or pokeweed mitogen. The present studies thus demonstrate that the virus plaque assay measures activated T-lymphocytes.A dissociation between the V-PFC response and cell proliferation was previously observed in antigen-stimulated cells cultured in the presence of mitotic inhibitors. In the present studies, while stimulation of CBA (H2(k)) lymphocytes by DBA/2 (H2(d)) cells produced high levels of thymidine incorporation, lymphocyte target-cell cytotoxicity, and V-PFC, stimulation of BALB/c (H2(d)) lymphocytes against DBA/2 (H2(d)) cells resulted in even higher levels of thymidine incorporation with a virtual absence of cytotoxic lymphocytes or V-PFC. These results indicate that proliferation is not a sufficient condition for permitting lymphocytes either to exert cytotoxicity on target cells or to replicate viruses, and suggest that there may be a correlation between the development of V-PFC and cytotoxic lymphocytes. They are consistent with the view that there are at least two functional subpopulations of T-lymphocytes.

Animals

Synergism between subpopulations of thymus-derived cells mediating the proliferative and effector phases of the mixed lymphocyte reaction.

The mixed lymphocyte reaction is characterized by proliferation and generation of specifically cytotoxic effector lymphocytes. These two phases of the mixed lymphocyte reaction have been shown to be mediated by distinct subpopulations of thymus-derived cells. The current investigation demonstrates that combinations of cells from thymus and lymph nodes of CBA mice exhibit synergism with respect to proliferation and effector cell production in response to Balb/c alloantigens. That is, the magnitude of the proliferative and effector phases of the mixed lymphocyte reaction exhibited by combinations of thymus cells and lymph node cells was greater than that given by equal numbers of the two cell types cultured separately. This cooperative interaction between lymphoid cell subpopulations in the mixed lymphocyte reaction parallels that which is responsible for the graftversus-host reaction. It is proposed, therefore, that the mixed lymphocyte reaction provides an in vitro model for the study of in vivo thymus cell interactions occurring in the graft-versus-host reaction.

Animals

Isogeneic lymphocyte interaction: recognition of self antigens by cells of the neonatal thymus.

Cells with the ability to recognize self antigens have been demonstrated in the thymus of the neonatal mouse. The detection of these cells is based upon a newly described in vitro phenomenon termed the isogeneic lymphocyte interaction. This interaction is demonstrable by [(14)C]thymidine uptake in cultures containing mixtures of neonatal thymus cells and adult spleen cells from the CBA strain of mice. The response observed in these mixtures has been shown to be almost entirely due to thymic cell proliferation. Other isogeneic lymphoid cells cannot replace adult spleen cells. Thymic isogeneic lymphocyte interaction activity increases sharply after birth, begins to decline within the first week of life and is lost by adulthood. It is suggested that the isogeneic lymphocyte interaction may represent an in vitro model for cognitory and discriminatory cellular events occurring routinely in vivo.

Animals