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Biomedical subjects

D D Isaak

Publications and source records attributed to D D Isaak.

11 recordsLinked to original sources
PubMed1991

Inhibition of antigen- and mitogen-induced activation of mouse splenocytes by uterine secretions from pregnant and progesterone-treated ewes.

Pregnant and progesterone-treated, ovariectomized ewes accumulate secretory products in the uterus that are immunosuppressive in mitogen-stimulated and mixed lymphocyte sheep cell cultures. In this study, uterine secretions from pregnant (Preg-UTM) and progesterone-treated, ovariectomized (P-UTM) ewes were equally effective in suppressing 3H-Tdr incorporation in mouse spleen cells stimulated with PHA. P-UTM inhibited PHA-stimulated, purified T-cells and separated L3T4+ and Lyt2+ T-cell subpopulations more than Preg-UTM, however. Both fluids were slightly inhibitory to conA-stimulated mouse spleen cells, enriched T-cells, and Lyt2+ T-cells but neither inhibited L3T4+ T-cells. For LPS-stimulated cells, P-UTM caused more suppression than Preg-UTM of enriched B-cells; however, suppression was similar for the two fluids on unseparated splenic cells. In antigen-stimulated mouse spleen cell cultures, both fluids inhibited antibody-forming cell responses to sheep erythrocytes, a thymus-dependent antigen, but neither suppressed antibody-forming cell responses to TNP-Ficoll, a thymus-independent antigen. These data indicate that uterine secretions in the ewe produced under the influence of progesterone or pregnancy contain immunoregulatory molecule(s) which modulate the activity of both homologous sheep and unrelated mouse lymphocytes. These studies establish the mouse as a useful in vivo model for studying the biological actions of these molecules.

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PubMed1989

T-cells inhibit Friend murine leukemia virus infection of B-cells in vitro.

The ability of splenic T-cells to regulate Friend murine leukemia virus replication in lipopolysaccharide-activated target B-cells infected in vitro was investigated. Removal of the T-cell fraction from spleen cells resulted in an 8- to 10-fold enhancement in the number of productively infected cells in the remaining B-cell-enriched fraction, as compared with unseparated spleen cells, and the addition of increasing numbers of purified T-cells to isolated B-cells prior to infection resulted in a directly proportional reduction in the number of B-cells releasing infectious progeny virus. Separation of splenic T-cells into Lyt 2- and Lyt 2+ T-cells before addition to infected B-cell cultures resulted in inhibition of infection only with the Lyt 2- T-cells; Lyt 2+ T-cells did not inhibit infection, even at high 1:1 ratios. Similarly, separation of splenic T-cells into L3T4+ and L3T4- T-cells before addition resulted in inhibition by L3T4+ but not L3T4- T-cells. Also, cytotoxic treatment of splenic T-cells with monoclonal anti-L3T4 antibody and complement before addition to B-cell cultures destroyed the regulatory effects. Finally, depletion of macrophages from both T-cells and B-cells before infection and coculture had no effect on the ability of T-cells to regulate B-cell infection. Collectively these results demonstrate that L3T4+ T-cells can inhibit Friend murine leukemia virus replication in target B-cells. Culture of isolated splenic T-cells with Friend murine leukemia virus in vitro resulted in the induction of alpha/beta but not interferon-gamma synthesis and in some experiments interferon-containing supernatants from T-cell-virus cultures were able to mediate suppression of B-cell infection with Friend helper virus; the addition of antibody specific for interferon-alpha/beta to cultures inhibited the ability of T-cells to regulate B-cell infection.

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PubMed1988

Decreased pathogenicity of murine leukemia virus-Moloney in gnotobiotic mice.

Newborn germ-free (GF) and conventional (CV) BALB/c mice were infected with murine leukemia virus-Moloney (MuLV-M) and subsequently monitored for virus expression and leukemia development. GF mice expressed more than 10-fold less virus in peripheral blood compared with CV mice, despite equivalent numbers of infected cells in the spleens, lymph nodes, thymi, and bone marrow of both groups. In addition to lower levels of virus expression, the latency period before the onset of fatal leukemias was greatly extended in GF mice; the first and last fatalities were recorded at 25 and 43 weeks postinfection, respectively, with a mean survival time of approximately 36 weeks. In CV mice, the first and last fatalities occurred at 8 and 17 weeks, respectively, with a mean survival time of approximately 13.5 weeks. Finally, the gross pathology of involved lymphoid organs varied in the two groups. GF mice experienced severe splenomegaly with or without lymphadenopathy but without thymoma; CV mice, in contrast, developed splenomegaly, lymphadenopathy, and severe thymoma. Collectively, these results indicate a marked resistance of GF animals to MuLV-M and suggest that the level of immune system activation may influence the pathogenicity of nontransforming retroviruses.

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PubMed1979

Inhibition of in vitro Friend murine leukemia virus infection of lipopolysaccharide-activated B-cells with concanavalin A.

Stimulation with bacterial lipopolysaccharide (LPS) of splenic B-lymphocytes infected in vitro with Friend virus complex increased the number of cells with replicating murine leukemia virus (MuLV) [i.e., infectious centers (IC)] up to 100-fold. Concanavalin A (Con A) did not have such an effect. However, the addition of Con A to the LPS-stimulated cultures decreased the number of IC. The inhibitory concentration of Con A (2.5 microgram/ml) was eightfold less than that capable of neutralizing the in vitro infectivity of MuLV (20 microgram/ml). The effect of Con A was not mediated by T-cells; the inhibition of infection was comparable with use of whole spleen cell suspensions from normal BALB/c mice, with T-cell-depleted cell suspensions, or with spleen cells with congenitally athymic nude mice. However, specific removal of Con A from the surface of B-cells with alpha-methyl-D-mannopyranoside prior to the infection reversed the inhibitory effect entirely. It is suggested that the lectin interferes with MuLV on the membrane of B-cells.

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PubMed1977

The course of Hymenolepis nana infections in thymus-deficient mice.

The kinetics of infection with Hymenolepis nana was examined in normal thymus-deficient mice. Following inoculation with 5 cyticercoids, the number of adult lumen-dwelling H. nana in congenitally thymus-deficient (nude) mice ultimately was at least 75 times the maximum infection intensity of normal thymus-bearing mice or thymus-reconstituted nude mice. Similar results were obtained following inoculation of H. nana eggs into nude mice; although thymus-bearing mice eliminated their infections, nude mice harbored more than 1,000 adult worms throughout the 7 weeks of the experiments. These data show that in mice, immunity is not generated against H. nana in the absence of thymus function. The data also confirm and establish the requirement of cysticercoid development in the intestinal mucosa for stimulation of a protective immune response against H. nana.

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PubMed1975

Thymus dependence of tapeworm (Hymenolepis diminuta) elimination from mice.

Although normal mice eliminated the lumen-dwelling intestinal cestode Hymenolepis diminuta by day 21 post-cysticercoid inoculation, congenitally thymus-deficient (nude) mice maintained their work burdens. Nude mice grafted with thymus glands or injected with thymus cells eliminated their worms.

Animals↗
PubMed1975

Studies on the immune response of congenitally athymic (nude) mice.

The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena.

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