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J Clagett

Publications and source records attributed to J Clagett.

24 records · Page 2Linked to original sources

Phytohemagglutinin-induced differentiation and blastogenesis of precursor T cells from mouse bone marrow.

The cells in mouse bone marrow (BM) capable of responding to phytohemagglutinin (PHA) were shown to be precursor T cells in experiments employing athymic mice, immunofluorescence, and specific lysis of T or B cells with cytotoxic antisera + complement. In contrast, the responses of lymph node (LN) and spleen (Spl) cells to this mitogen were shown by the same techniques to rely upon resident populations of mature T lymphocytes in these peripheral lymphoid organs. Cytolysis of T cells with anti-theta (anti-Thy 1), anti-thymocyte, or anti-brain antisera abolished the PHA responses of LN and Spl, but had no appreciable effect on the BM PHA response. Lysis of B cells with anti-mouse gamma globulin or anti-mouse IgM antisera had no significant effect on either Spl or BM blastogenesis in response to this lectin. Immunofluorescent studies with fluoresceinated anti-brain sera demonstrated acquisition of T-cell surface antigens by BM null lymphocytes during the blastogenic response of this tissue to PHA. The results of these immunofluorescence experiments were reproducible even when marrow obtained from nude mice and pretreated with anti-brain serum plus complement was employed. The implications of these findings with regard to prophylaxis against graft versus host disease in BM transplant recipients are discussed.

Animals↗

Mitogenic activity of Actinomyces viscosus. I. Effects on murine B and T lymphocytes, and partial characterization.

Actinomyces viscosus homogenate (AVIS) contins substance(s) which cause spleen cells from conventional and germfree mice to undergo increased DNA synthesis. This mitogenic effect is primarily on B cells since spleen cells from nude mice or T-depleted spleen cells from conventional mice respond as strongly as conventional (T + B) spleen cells. Mouse thymocytes do not respond mitogenically to AVIS. It is unlikely that the mitogenic acitivity is due to the presence of LPS, since A. viscosus is Gram-positive and is not known to have an LPS cell wall component. Also, AVIS is not inactivated by polymyxin B, as are some preparations of LPS, and C3H/HeJ mouse splenocytes respond strongly to AVIS but not to LPS. The activity is heat stable, is not lost upon dialysis, and is not affected by lysozyme. Mitogenic activity is partially lost when AVIS is digested with nonspecific bacterial protease or treated with metaperiodate. Sodium hydroxide treatment completely abolishes mitogenic activity. Actinomycotic lesions are characterized by a long-tern inflammatory response involving a dense plasma cell infiltrate. We suggest that B cell mitogens form Actinomyces may play a role in the elicitation of the plasma cell component of these lesions.

Actinomyces↗

Sequences related to immunoglobulin kappa chain messenger RNA in T cells.

We investigated by molecular hybridization whether T cells contain RNA sequences homologous to RNA which codes for immunoglobulin kappa-chain (k-chain). A radioactive probe of complementary DNA (cDNA) was prepared by transcription of purified k-chain mRNA from mouse myeloma MOPC-41 with reverse transcriptase (RNA-dependent-DNA nucleotidyltransferase) from avian myeloblastosis virus. The cDNA probably corresponded only to the constant region and 3'-terminus of k-chain mRNA. Kappa-chain cDNA was found to hybridize efficiently with RNA from both thymus cells and an established culture of thymoma cells. The thymus and thymoma cells contained 99.8% and 100% theta-positive cells, respectively. Quantitatively the average thymus T cell (thymus derived lymphocyte) contained about one half as much k-chain mRNA as the average spleen B cell ("bursa" dependent lymphocyte), whereas the thymoma cells contained only 1/33 as much. Control hybridizations of k-chain cDNA with myeloma and liver RNA support the conclusion that T cells in the thymus and in the thymoma cell line synthesize k-chain mRNA-like molecules. The thermal stability of hybrids of k-chain cDNA with RNA from spleen, thymus, thymoma, and another k-chain producing myeloma tumor was lower than that with MOPC-41 RNA. This finding may be due to the existence of several slightly different ck genes in the mouse as suggested by various control experiments.

B-Lymphocytes↗

In vivo and in vitro studies on possible pathogenic mechanisms of Actinomyces viscosus.

Actinomycotic infections are characterized by long-term inflammatory lesions containing large numbers of polymorphonuclear leukocytes (PMNs) and mononuclear cells. The pathogenic mechanisms involved in these lesions are not understood. Homogenates of Actinomyces viscosus (AVIS) induce an acute inflammatory response with a predominance of PMNs within 6 h after injection into the footpads of nonimmunized mice. These homogenates, when tested in vitro, contain potent chemotactic activity for human PMNs. In vitro chemotactic activity for human monocytes is weak but statistically significant (P less than 0.025). Doses of AVIS, which alone have little chemotactic activity, cause the generation of PMN chemotactic activity in fresh, but not complement-inactivated, serum. The injection of AVIS into the footpads of immunized mice induces an acute inflammatory response followed within 48 h by a mononuclear cell infiltrate, suggesting that factors affecting monocyte accumulation are generated by the immune host in response to challenge with the bacterial antigens. These findings indicate that the pathogenicity of the Actinomyces may result in part from (i) their direct chemotactic effect on PMNs, (ii) their cytotaxigenic effects on serum, and (iii) their ability to stimulate host immune cells to produce and release mediators of inflammation.

Actinomyces↗