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K D Elgert

Publications and source records attributed to K D Elgert.

At least 55 records · Page 3Linked to original sources
PubMed1986

Splenocytes from tumor-bearing Corynebacterium parvum treated mice maintain interleukin-2 and -3 activity.

Systemic and local administration of the bacterium Corynebacterium parvum (more accurately known as Propionibacterium acnes) is reported to exert antitumor action via activated macrophages or short-lived cytotoxic T lymphocytes (CTL), respectively. This study examined the effect of C. parvum treatment on resulting in vitro interleukin levels, which are components in the sequence of events leading to the development of effective CTL. C. parvum administration prevented palpable fibrosarcoma development. This was concomitant with restoration and maintenance of normal interleukin-2 (IL-2) and interleukin-3 (IL-3) levels and prevention of suppressor cell development in mice injected with both tumor cells and vaccine. Our finding of C. parvum-induced maintenance of IL-2 and IL-3 levels and apparent lack of suppressor cell formation lends support to the idea of local C. parvum antitumor action possibly being mediated by CTL arising via the interleukin cascade.

Animals↗
PubMed1986

An improved data analysis method for interleukin 2 microassay.

Development of the interleukin 2(IL 2) microassay, coupled with the use of highly purified or recombinant factors has allowed a detailed examination of the mechanism of action of this important biological response modifier. However, probit analysis of the microassay data does not allow inherent error of the system to be approximated nor can units of activity be assessed for significance. A computer program was developed to analyze the validity of each regression line and to generate 95% confidence intervals around each line. This program employs analysis of variance, linear regression analysis and the parallel line assay to fix confidence intervals for each IL 2 unit value. The use of recombinant IL 2 as an immunomodulator in clinical settings warrants a more precise statistical method to evaluate normal fluctuations of this factor than currently in use. The development of such a method is presented here.

Biological Assay↗
PubMed1984

Interleukin 2 (IL-2) activity during tumor growth: IL-2 production kinetics, absorption of and responses to exogenous IL-2.

A temporal study assessed the relationship between fibrosarcoma growth and immunologic encumbrance due to the inability of BALB/c mouse splenocytes to elaborate the lymphokine Interleukin 2 (IL-2). Nylon-wool fractionation and antiserum treatments suggested the existence of a mildly nylon-wool-adherent, anti-Lyt 2-sensitive tumor-induced suppressor T (Ts) cell which significantly decreased IL-2 activity. Absorption investigations indicated that ligand-activated tumor-bearing host (TBH) spleen cells were less receptive to IL-2 than their normal counterparts. When splenocytes were antiserum treated before absorption, removal of Lyt 2+ (suppressor T) cells resulted in greater IL-2 absorption by the remaining cells. Purified IL-2 only partially restored suppressed TBH spleen cell mitogen- or alloantigen-induced blastogenesis; whereas, normal host reactivity was significantly augmented. The collective data suggest that TBH spleen cells were capable of producing IL-2 and of responding to the IL-2 amplification signal when tumor-induced Ts cells were depleted.

Absorption↗
PubMed1984

In vivo assessment of tumor-induced nonspecific suppression of contact sensitivity. II. Regulation by cytokines and T cells via adoptive transfer.

Normal BALB/c mice were assessed for 2,4-dinitrofluorobenzene (DNFB)-induced contact sensitivity following adoptive transfer of macrophages (Mo). T cells, or their derived products, from normal or tumor-bearing hosts (TBH). Contact sensitivity (CS) was measured by a quantitative radioisotopic ear assay, a total in vivo system based on localization of IP-injected iodinated human serum albumin [( 125I]HSA) in the DNFB-challenged ear. Adoptive transfer of low or high doses of TBH T cells or their derived supernatants into normal recipients suppressed their responsiveness, while Mo supernatants enhanced it. Moreover, in all cases adoptive transfer of TBH cells or supernatants resulted in a lower CS response than did their normal counterparts. These results further corroborate our previous in vitro data indicating that T cells, or Mo and T cell soluble products, possess immunoregulatory capabilities in vivo.

Animals↗
PubMed1984

Macrophage-derived prostaglandin E modulation of the mixed-lymphocyte reaction: an anomaly of increased production and decreased T-cell susceptibility during tumor growth.

One-way mixed-lymphocyte reactions (MLR) were used to assess macrophage (M phi)-derived factor-mediated modulation of normal and tumor-bearing host (TBH) T-cell immune responsiveness. Normal and TBH M psi culture supernatants contained the inhibitory substance prostaglandin E (PGE) in concentrations of 10(-8) to 10(-9) M, with TBH M phi supernatant containing approximately twice the amount of PGE as its normal counterpart. Normal and TBH MLR reactivity were both suppressed by the addition of normal host M phi supernatant. However, TBH T cells were less inhibited by TBH M phi supernatant (55%) as compared to normal host T cells (73%). Although dialyzed M phi supernatants were less inhibitory (17-19%) on normal host T-cell MLR reactivity, TBH T-cell responses were enhanced (20-46%). Indomethacin or eicosatetraynoic acid treatment of M phi reduced PGE levels in the supernatants and in general enhanced MLR reactivity. When PGE1 and PGE2 were titrated in the MLR, normal host T lymphocytes were more susceptible to inhibition than were TBH. Concentrations of PGE1 and PGE2 comparable to that found in normal host M phi supernatants caused approximately 38% inhibition whereas whole M phi supernatants decreased MLR reactivity by greater than 70%, suggesting that another factor(s) was necessary to account for the additional M phi-mediated suppression of lymphocyte function. Isoelectric focusing was used to fractionate normal host M phi supernatant. Two factors with isoelectric points in the pH ranges 7.0-8.5 and 4.5-5.0 were inhibitory in the MLR. An enhancing factor was also identified with an pI in the range of pH 6.0-7.0. These data suggest that TBH M phi-derived PGE production was increased over its normal counterpart, but that TBH T cells were less susceptible to its effect and an additional factor(s) was working in concert with PGE.

Animals↗
PubMed1984

Normal and tumor-bearing host macrophage factor-mediated modulation of mixed-lymphocyte reaction responsiveness: separation of T-lymphocyte subset susceptibility to enhancing and inhibitory factors.

The mixed-lymphocyte reaction reactivity of normal and tumor-bearing host (TBH) T-cell subsets was examined in response to normal and TBH macrophage (M phi) supernatants. Both inhibiting and enhancing activities were identified in normal and TBH M phi supernatants. The present data suggest that TBH M phi supernatants contained more inhibitory activity than normal host M phi supernatants and that enhancing activity of M phi supernatants was restricted to the Lyt 2,3+ population of cells. TBH Lyt 2,3+ cells were more responsive to the enhancing molecule(s) than their normal counterparts. These data were consistent with studies which implicate M phi as being partially responsible for the immune dysfunction seen in TBH, and extends previous findings on the ability of M phi to regulate the immune response in an attempt to achieve homeostasis.

Animals↗
PubMed1984

Interleukin 3 activity in tumor-bearing hosts: decreased splenocyte production of and responsiveness to IL 3.

A kinetic study assessing the relationship between tumor growth and the ability of BALB/c mouse splenocytes to produce Interleukin 3 (IL 3) indicated a concomitant decrease in IL 3 activity with tumor growth. Tumor-bearing host (TBH) splenocytes produced 600 pmoles/hr/10(8) cells of IL 3 activity at Day 0 but only 62 pmoles/hr/10(8) cells by Day 28 post tumor cell inoculation. Nylon wool fractionation (to remove adherent suppressor cells) did not restore IL 3 activity. Addition of purified IL 3 to mitogen proliferation assays showed that IL 3 alone was mitogenic for normal host but not TBH splenocytes. In concert with concanavalin A (Con A) and phytohemagglutinin, IL 3 augmented in vitro normal host splenocyte responsiveness but significantly further suppressed it in the TBH. An absorption assay indicated that fresh cells had acceptors to remove IL 3 from supernatants. Con A-induced normal or TBH blast cells lost their ability to absorb IL 3. Intravenous inoculation of purified IL 3 into normal and TBH resulted in further suppression of TBH splenocyte mitogen-induced blastogenesis. The exacerbation of TBH spleen cell reactivity by IL 3 may be due to a tumor-induced feedback inhibition mechanism further suppressing cellular differentiation critical to cytotoxic T lymphocyte maturation.

Animals↗
PubMed1983

Immunoregulation of the mixed lymphocyte reaction by macrophage-derived factors: functional and biochemical separation of enhancing and inhibitory factors.

Positive and negative immunoregulation of the mixed lymphocyte reaction (MLR) occurred through release of macrophage(MO)-derived, soluble enhancing and inhibitory factors. Macrophages, sonicated or cultured in low concentrations, produced nondialyzable, soluble factor(s) capable of enhancing the MLR; but the culture supernatant had no biologically detectable levels of Interleukin 1, Interleukin 2, or interferon. Production of enhancing supernatants was not affected by pretreatment of MO with trypsin or anti-Thy 1 antibody plus complement. In contrast, MO cultured in high concentrations yielded an inhibitory supernatant factor(s) which suppressed MLR reactivity even when MO were cultured in the presence of indomethacin. Culturing MO with proteolytic enzyme inhibitors increased the yields of the inhibitory and enhancing factors. Both factors were precipitable with ammonium sulfate and could be separated into several biologically active fractions using anion exchange chromatography.

Animals↗
PubMed1983

Level of macrophage induction during tumor growth: primed or activated?

The activation level of thioglycolate (TG)-elicited peritoneal macrophages (Mphi) from normal and fibrosarcoma-bearing BALB/c mice was investigated. Lipopolysaccharide was used to distinguish in vitro levels of Mphi activation. The results of cytotoxicity assays, which measured nonspecific killing of P815 tumor cells by activated Mphi, indicated that tumor-bearing host Mphi were primed in situ while normal host Mphi remained in a resting state. This level of Mphi induction may contribute to the resulting tumor-bearing host T cell immune hyporesponsiveness.

Animals↗
PubMed1983

Conversion of normal host splenocytes to suppressor cells by tumor-induced suppressor T-cell-derived factor(s): cyclophosphamide treatment reverses inhibitory activity.

Suppressor T (Ts) cells (or their factors) that arise in BALB/c mice as a consequence of fibrosarcoma cell growth can be adoptively transferred and can recruit new regulatory cells in vitro. In vivo temporal studies indicated that Ts cells significantly inhibited blastogenesis in normal host splenocytes as early as 4 h after adoptive transfer and lasted as long as 5 days. Suppressor T-cell-derived factor(s) did not suppress until 24 h after in vivo administration, and effects were protracted beyond time periods observed with Ts cells. Supernatants containing suppressor factor(s) not only significantly inhibited normal host spleen cell proliferation but also induced and/or recruited cells to become suppressive. Cyclophosphamide treatment of tumor-bearing hosts restored their in vitro spleen cell blastogenic ability and abolished in vitro suppression by Ts cells or their factors. This was confirmed in vivo by passive transfer experiments. Macrophage removal seemed to augment cyclophosphamide's ability to eliminate suppression.

Animals↗
PubMed1981

Suppressor cell activity in tumor-bearing mice. III. Co-purification of a factor inhibiting cellular DNA synthesis and DNA polymerase activity.

The factor(s) derived from fibrosarcoma-induced suppressor T cells was sensitive to pronase and neuraminidase, but not to trypsin, beta-galactosidase, DNase, or RNase. Protein and RNA, but not DNA, synthesis were required to mediate suppression. Suppressor T cell-derived factor(s) could be precipitated by a 50% saturated ammonium sulfate (SAS) solution. The 50% SAS fraction inhibited both in vitro and in vivo spleen cell blastogenesis, whereas the 80% and unprecipitated fractions had no inhibitory activity. Using Sephadex G-200 chromatography, the 2nd protein fraction (fraction II) contained an inhibitor of both DNA polymerases (IDP) and DNA synthesis (IDS) activity, which possessed no cytotoxic activity. In vitro DNA polymerase alpha activity was suppressed by fraction II, whereas DNA polymerase beta and gamma activities remained unchanged. Molecular weight of IDP/IDS, as determined by Sephadex G-200 gel filtration chromatography, was approximately 14,500. Attempts to separate IDP/IDS activities found in fraction II by anion-exchange chromatography and slab gel electrophoresis were not successful, which suggested that the 2 activities were the same or very similar molecules.

Ammonium Sulfate↗
PubMed1980

Enhancement of T cell MLR reactivity by addition of macrophage supernatants from tumor-bearing mice.

One-way mixed lymphocyte reactions (MLR) were used to establish a correlation between loss of in vitro T cell reactivity and in vivo tumor growth. Though supernatants from anti-Thy 1 treated macrophages (M phi) greatly enhanced MLR activity in normal T cells, such addition had little effect in reversing the inability of T cells from 2-week palpable tumor-bearing mice (TBM) to recognize in vitro foreign histocompatibility antigens. Since normal T cells, exposed to TBM M phi supernatants, exhibited no decrease in proliferative response, TBM T cell loss of MLR reactivity could not be ascribed to tumor-induced suppressor M phi.

Animals↗
PubMed1980

Cell-mediated immunity in Marek's disease virus-infected chickens genetically selected for high and low concentrations of plasma corticosterone.

Lines of chickens genetically selected for high (HPC)-and low-plasma corticosterone (LPC) titers were assessed for cell-mediated immunity during Marek's disease tumorigenesis. Lymphocyte transformation (using phytohemagglutinin and 2,4-dinitrofluorobenzene-bovine serum complex) and mitogen-induced cellular cytotoxicity were evaluated with peripheral blood leukocytes. Chickens from the LPC line showed a greater lymphocyte transformation response than those from the HPC line. All tumor-bearing chickens demonstrated a markedly suppressed blastogenic response. Although the blastogenic response was suppressed in those chickens infected with Marek's disease virus but not having gross tumors when compared with the steroid level, this response was greater than that of chickens with tumors and less than that of normal controls. In comparison with LPC-line chickens, HPC-line chickens demonstrated a decreased mitogen-induced cellular cytotoxicity. A decreased mitogen-induced cellular cytotoxicity was observed in both steroid lines concomitant with the onset and severity of tumors. The impaired cell-mediated response observed in the HPC line was associated with an increased tumor incidence and a greater mortality than that observed in the LPC line. Metyrapone, a chemical which blocks adrenal corticosterone synthesis, transiently enhanced mitogen-induced cellular cytotoxicity and initiated tumor regression in chickens debilitated with Marek's disease tumors.

Animals↗