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E M Goodell

Publications and source records attributed to E M Goodell.

10 recordsLinked to original sources
PubMed1990

Conditioned medium from activated rat macrophages and the recombinant factors, IL-1 beta and GM-CSF, enhance the accessory activity of dendritic cells.

Low density lymph node cells (LD-LNC; 5% of total unfractionated LNC) contain 95% of the accessory activity required for responses of T lymphocytes to mitogens. Significantly greater responses to mitogens occur when T lymphocytes are added to LD-LNC that have been exposed overnight to silica, in comparison to responses occurring with LD-LNC incubated without silica. Conditioned medium (CM) from silica-treated LD-LNC is itself able to mediate enhanced responses; i.e., when LD-LNC are exposed overnight to CM alone and mitogen-treated T lymphocytes added the next day. The enhancing activity found in CM from LD-LNC exposed to silica is produced by macrophages; however, their low accessory activity is not enhanced by CM. In contrast, dendritic cells isolated from LD-LNC exposed to silica or to CM show significantly increased accessory activity, but dendritic cells do not produce the enhancing activity found in CM. CM lacks IL-2 activity and does not have any effect on the responses of untreated or mitogen-treated T lymphocytes alone. Thus, macrophages produce the enhancing activity and dendritic cells respond to it. Maximum enhancement of dendritic cell accessory activity requires overnight exposure to CM; once induced, accessory activity is not further modulated after continued incubation in the presence or absence of CM. LD-LNC, adherent peritoneal exudate cells, and adherent thioglycollate-induced peritoneal exudate cells produce enhancing activity after exposure to silica, LPS, and silica plus LPS. After gel filtration of a CM produced by silica plus LPS, enhancing activity shows a broad molecular weight distribution between 20 and 55 kD. IL-1 is present in CM and shows a more narrow molecular weight distribution that falls within the lower molecular weight range for enhancing activity. Silica treatment by itself produces CM containing little IL-1, but abundant enhancing activity; gel filtration of this CM shows that the distribution of enhancing activity is confined more narrowly to the higher molecular weight range, suggesting that IL-1 is one of several factors that enhances the accessory activity of dendritic cells. Recombinant human IL-1 beta does have enhancing activity, but of the other recombinant factors tested only mouse GM-CSF also has enhancing activity. Human IL-1 alpha, tumor necrosis factor alpha, IL-4, rat IL-3 and rat IFN-gamma, as well as L cell-conditioned medium containing M-CSF, lack enhancing activity.

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PubMed1988

The effect of silica treatment on accessory cell-dependent rat T lymphocyte proliferation.

Previous work has shown that purified rat macrophages lack both accessory activity for T lymphocyte responses to mitogens and stimulatory activity in a mixed leukocyte reaction, in marked contrast to the potent activity of dendritic cells. This study was designed to re-evaluate macrophages as accessory cells by treating various cell preparations with either silica or L-leucine methyl ester, which have been reported to be toxic to macrophages, and then determining the effect of the treated cells on responses to the mitogens, sodium periodate or concanavalin A. These studies indicated that treatment with L-leucine methyl ester failed to kill rat macrophages or dendritic cells, whereas silica was specifically toxic for rat macrophages. The studies therefore focused on silica. Co-culturing mitogen-treated lymph node cells with silica over a wide range of concentrations had no effect on responses. The same results were obtained if mitogen-treated lymphocytes were enriched with lymph node macrophages and dendritic cells and then co-cultured with silica. Preparations containing both macrophages and dendritic cells were incubated with silica for 24 h to ensure the death of virtually all macrophages; upon the addition of mitogen-treated lymphocytes, the macrophage-depleted accessory cells induced vigorous proliferative responses. Peritoneal exudate cells showed variable, but low accessory activity that increased after incubation with silica. Elimination of more than 90% of the macrophages from peritoneal exudate cells, as determined by staining for non-specific esterase, failed to eliminate this accessory activity. Taken together, these findings confirm and extend the conclusion that rat macrophages lack or have exceedingly low accessory activity.

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PubMed1988

Dendritic cells from rat lung are potent accessory cells.

Accessory cells are required for the induction of lymphocyte proliferation in response to mitogens or antigens. Rat pulmonary cells were tested for the presence of accessory activity in lymphocyte proliferation induced by sodium periodate. Buffer-perfused lungs were excised, minced, and enzymatically digested. The resulting pulmonary cells (PC) were separated into high density (HD-PC, 32 to 57%) and low density (LD-PC, 9 to 32%) fractions in a discontinuous density gradient of bovine plasma albumin (BPA). Both macrophages and dendritic cells were observed in the LD-PC by light microscopy. HD-PC, LD-PC, adherent LD-PC, nonadherent LD-PC, and a purified preparation of pulmonary dendritic cells (DC-P) were tested for accessory activity in the presence of periodate-treated, lymph-node-derived lymphocytes as responders. Most of the accessory activity was found in the LD-PC. Increasing numbers of LD-PC stimulated proliferation of responder lymphocytes in a linear, dose-dependent manner; higher numbers had a suppressive effect. Nonadherent LD-PC containing dendritic cells also produced a dose-dependent increase in periodate-induced lymphocyte proliferation, whereas adherent LD-PC, morphologically identified as macrophages, were suppressive. Removal of phagocytic macrophages from nonadherent LD-PC resulted in an eightfold increase in both the percent of DC-P present and the amount of accessory activity in the LD-PC. We conclude that pulmonary dendritic cells are potent accessory cells for periodate-induced lymphocyte proliferation.

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PubMed1987

Accessory cell dependent T lymphocyte proliferation: potent activity of dendritic cells.

The proliferative response of T lymphocytes to Concanavalin A (Con A) and the oxidative mitogens, sodium periodate (NaIO4) and neuraminidase plus galactose oxidase (NGO), requires the participation of dendritic cells (DC). High density cells (HDC) recovered from the fractionation of lymph node cells on a discontinuous gradient of bovine plasma albumin did not respond to NaIO4, but responded well above background levels to NGO or Con A. Addition of DC elevated these responses further. By an indirect panning technique, the HDC were exhaustively depleted of cells expressing Ia surface antigens. Ninety-nine percent of these HDC displayed T cell surface antigens. These Ia- T cells did not respond to any of the three mitogen treatments until DC were added, whereupon the proliferative responses were restored in a concentration-dependent manner, with maximal levels attained at a DC to T cell ratio of 1:200. The addition of a purified preparation of IL2 to untreated or mitogen-treated Ia- T cells increased the proliferative responses slightly and was unable to substitute for the potent activity of dendritic cells. Only the addition of DC was able to stimulate mitogen-induced proliferation to maximal levels. The limiting factor in these responses was the number of dendritic cells, which controlled the induction of both the release of IL2 and responsiveness to IL2 for the oxidative mitogens and Con A. Thus, DC function as potent accessory cells for each of the three mitogens.

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PubMed1987

Immunologic, morphologic, and functional evaluation of long-term-surviving beagle lung allograft recipients treated with lethal total-body irradiation, autologous bone marrow, and methotrexate.

Immunologic, morphologic, and functional evaluations were performed in beagle dogs with single lung allografts surviving 3-13 years after transplantation. Immunosuppressive treatment included lethal total-body irradiation, autologous bone marrow reconstitution, and three doses of methotrexate. Three beagle recipients with full DLA-haplotype-matched grafts and five recipients with one-haplotype-mismatched grafts were studied. Evidence of rejection--i.e., infiltrates on chest roentgenograms, hypoperfusion on radionuclide lung scans, and histopathologic changes--were absent in the matched recipients and in three of the five mismatched recipients. Two of the mismatched recipients had decreased perfusion to their allografted lungs, and open-lung biopsy specimens revealed diffuse fibrotic blood vessels with narrowed lumina but no other abnormalities. Decreased fractional blood flow to the lung allograft of the five one-haplotype-mismatched recipients was correlated (r = -0.92) with the level of donor-specific cytolytic lymphocyte activity generated in mixed lymphocyte cultures (MLC). In contrast, the level of proliferative activity in donor-specific MLC did not correlate well with graft function. These findings suggest that the mechanism of tolerance to these lung allografts (with particular regard to vascular integrity) involves attenuation of the response against major histocompatibility complex (MHC) class I alloantigen since the induction of cytolytic T lymphocytes in MLC is directed primarily against these molecules. Though all of the mismatched recipients had the ability to react against MHC class II alloantigens in vitro (as demonstrated by proliferative responses in MLC), in vivo responses to class II gene products may not occur because of the lack of expression of these molecules on long-term surviving grafts.

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PubMed1985

Canine dendritic cells from peripheral blood and lymph nodes.

Canine dendritic cells were prepared from peripheral blood or lymph nodes using a series of steps including fractionation on bovine plasma albumin (BPA), irradiation with 4000 R, incubation for 16-18 hours, and refractionation on BPA. Dendritic cells were recovered in the low density (LD) fraction containing approximately 0.6% of the unfractionated cells. Measured by the incorporation of 3H-thymidine, the response of the high density (HD) cells to neuraminidase-galactose oxidase (NGO) was lower than that of the unfractionated lymph node cells (LNC) but increased in a concentration dependent manner after the addition of a population of cells enriched for dendritic cells (30-70% by morphologic criteria). Cooperation between HD- and LD- cells was not restricted to identity of the major histocompatibility complex. Canine dendritic cells also displayed stimulatory activity higher than unfractionated peripheral blood mononuclear cells (PBMC) in a one way mixed leukocyte culture (MLC). Canine dendritic cells were nonadherent to plastic, were of low density, and remained viable and functional after irradiation. For the first time, canine dendritic cells have been identified in peripheral blood and lymph nodes and have been shown to act as accessory cells in the response of lymphocytes to NGO and as stimulator cells in a MLC.

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PubMedDate not supplied

Dendritic cell ontogeny.

Abundant evidence indicates that dendritic cells arise from the bone marrow. In vitro, precursors that differ phenotypically from mature dendritic cells divide several times to form functional dendritic cells. A soluble factor(s) produced in the supernatants of ConA-stimulated spleen cells enhances the production of dendritic cells. This factor(s) has not been fully characterized. Further maturation of dendritic cells occurs after they are released from the bone marrow; species differences exist. Interrelationships between various types of dendritic cells need to be elucidated.

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