scholarly journals Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells.

1987 ◽  
Vol 165 (2) ◽  
pp. 515-530 ◽  
Author(s):  
S L Koide ◽  
K Inaba ◽  
R M Steinman
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cell Function ◽  
Interleukin 1 ◽  
Peritoneal Macrophages ◽  
Lymphocyte Culture ◽  
Con A ◽  
Helper T Lymphocytes ◽  
Accessory Cells ◽  
Amplifying Effect

The function of exogenous murine recombinant IL-1 alpha as a T lymphocyte-activating molecule was examined. IL-1 did not induce IL-2 release or responsiveness in purified T cells regardless of their state of activation: unprimed lymphocytes, freshly sensitized lymphocytes, or memory cells derived from the blasts. Nor did IL-1 synergize with mitogens, or with antigens, to stimulate proliferation. For example the combinations of IL-1 plus Ia+ peritoneal macrophages, or IL-1 plus Con A, were less than 5% as effective in triggering T cell growth as a low dose (1%) of dendritic cells. However, when IL-1 was added at the onset of culture, the response to limiting doses of dendritic cells was increased 3- to 10-fold in several systems: the syngeneic and allogeneic MLR, Con A- and periodate-induced polyclonal mitogenesis, and T-dependent antibody formation against foreign red cells. The amplifying effect of IL-1 could be obtained if the dendritic cells but not the responding lymphocytes were exposed to IL-1 before use as accessory cells. Optimal activation of dendritic cells required a dose of 5 U/ml (50 pM) and 18 h of exposure, and was not due to carryover of IL-1 into the lymphocyte culture. IL-2, IL-3, and cachectin/TNF did not amplify dendritic cell function, while IFN-gamma diminished it. The enhanced function of IL-1-treated dendritic cells was due to an enhanced clustering with helper T lymphocytes in the first day of the MLR response. Therefore IL-1 does not seem to act as an activating factor for most peripheral T lymphocytes. Instead, IL-1 enhances the function of accessory dendritic cells and represents the first molecule that has been shown to enhance the immune response at this critical level.

scholarly journals The function of Ia+ dendritic cells and Ia- dendritic cell precursors in thymocyte mitogenesis to lectin and lectin plus interleukin 1.

1988 ◽  
Vol 167 (1) ◽  
pp. 149-162 ◽  
Author(s):  
K Inaba ◽  
M D Witmer-Pack ◽  
M Inaba ◽  
S Muramatsu ◽  
R M Steinman
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Interleukin 1 ◽  
Peritoneal Macrophages ◽  
Accessory Cell ◽  
Con A ◽  
Thymocyte Proliferation ◽  
Accessory Function ◽  
Accessory Cells ◽  
Macrophage Colony

The response of thymocytes to lectin is a standard tissue culture model for identifying cytokines such as IL-1 that are required for thymocyte mitogenesis. To study accessory cell requirements for these responses, it was necessary to deplete endogenous accessory cells with two techniques: anti-Ia and complement, and passage over nylon wool. Proliferation to Con A was then restored with 0.1-0.3% exogenous splenic dendritic cells, or 30-fold higher levels of peritoneal macrophages. The "costimulatory" action of IL-1, whereby responses to lectin were enhanced 3-10-fold, required the presence of dendritic cells. This effect of IL-1 could be reproduced by culturing the dendritic cells for 12 h in 1 U/ml human or murine rIL-1 alpha before addition to the thymocyte proliferation assay. The function of IL-1-treated dendritic cells was not blocked by a neutralizing anti-IL-1 antibody. The endogenous population of thymic accessory cells was partially characterized. A trace (0.1-0.3%) fraction of Ia+, Ig-, plastic nonadherent dendritic cells was visualized and enriched to a level of 1-10% by depleting CD4+,CD8+, and Ig+ lymphocytes. When this double-negative population was cultured with IL-1 and washed, the treated thymic dendritic cells were 10-fold more active as accessory cells. When the CD4-,CD8-, Ig- populations were depleted of dendritic cells with anti-Ia and complement, the subsequent addition of IL-1 had a second effect. Ia+ dendritic cells redeveloped over a 2-d interval, and they exhibited the same properties as resident dendritic cells in thymus and spleen. The majority were lysed by 33D1 anti-dendritic cell mAb and complement, lacked Fc receptors, and acted as powerful stimulators of the MLR and Con A mitogenesis. The development of dendritic cells did not occur with IL-2, -3, -4 or granulocyte/macrophage colony-stimulating factor or in nylon-nonadherent populations. The IL-1-dependent, Ia- precursor was not detectable in bone marrow. These results begin to analyze the endogenous accessory function of the thymus in culture. Dendritic cells actively stimulate thymocyte mitogenesis. The mitogenic action of IL-1 involves effects on resident Ia+ dendritic cells as well as a new population of thymic, Ia- precursors.

scholarly journals Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes.

1980 ◽  
Vol 152 (4) ◽  
pp. 1070-1084 ◽  
Author(s):  
M C Nussenzweig ◽  
R M Steinman ◽  
B Gutchinov ◽  
Z A Cohn
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cell Function ◽  
Accessory Cell ◽  
Similar Treatment ◽  
Peritoneal Cells ◽  
Accessory Cells ◽  
Nylon Wool

This study establishes that dendritic cells (DC) are the critical accessory cells for the development of anti-trinitrophenol (TNP) cytotoxic T lymphocytes (CTL) in vitro. We developed a model in which nylon wool-nonadherent spleen cells were used both as the responding and stimulating cells, the latter having been TNP-modified and x-irradiated. Thy-1-bearing CTL developed in C57BL/6, B6D2F1, and CBA mice only when small numbers of DC were added. Maximal responses in 5-d cultures were achieved with 0.5-1 DC/100 responding T cells. The DC did not have to be TNP modified directly. Anti-Ia and complement inactivated accessory cells, whereas similar treatment of the responders had no effect. DC exposed to ultraviolet radiation were ineffective, but x-irradiated DC were fully active. Culture media from DC, or from DC-nylon wool-passed spleen T cell cocultures that contained abundant CTL, would not substitute for viable DC. Enriched preparations of macrophages (M phi) were obtained from blood, peritoneal cavity, and spleens of BCG-immune and unprimed mice. M phi added at doses of 0.2-4% were weak or inactive as accessory cells. The level of Ia antigens on test M phi populations was quantitated and visualized by binding of a radioiodinated monoclonal anti-I-Ab,d antibody, clone B-21. M phi that bore substantial amounts of Ia from all organs were weak accessory cells. Addition of M phi to DC-T cell cocultures produced inhibitory effects, usually at a dose of 2% M phi. In contrast, 0.5% Ia-bearing M phi from BCG-immune boosted mice inhibited > 80% of the DC-mediated CTL response. Addition of indomethacin reversed M phi inhibition, and 10(-9) M prostaglandin E2 in turn blocked the indomethacin effect. Indomethacin also restored a low level of accessory cell function in immune-boosted adherent peritoneal cells, but not in preparations of monocytes and spleen M phi. Small numbers of DC were identified in preparations of immune-boosted peritoneal cells and may have accounted for the observed accessory activity. We conclude that the development of anti-TNP CTL is an immune response in which (a) DC are the critical accessory cells; (b) Ia-bearing M phi are weak or inactive; and (c) M phi can inhibit DC-mediated response by an indomethacin-sensitive mechanism.

scholarly journals Induction of interleukin 1 alpha mRNA during the antigen-dependent interaction of sensitized T lymphoblasts with macrophages.

1988 ◽  
Vol 168 (1) ◽  
pp. 409-416 ◽  
Author(s):  
S Koide ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Interleukin 1 ◽  
Cdna Probe ◽  
Class Ii ◽  
Third Party ◽  
Con A ◽  
Class Ii Mhc ◽  
T Lymphoblasts

DNA-RNA hybridization with an IL-1 alpha cDNA probe was used to monitor the induction of IL-1 in macrophages that were acting as accessory cells for the proliferation of T lymphocytes. Mouse peritoneal macrophages bound and stimulated T lymphocytes in the presence of the mitogens, Con A, or anti-CD3 mAb, but little or no IL-1 mRNA was detectable. In contrast, if the T cells were first sensitized in a mixed leukocyte reaction with dendritic cells and then added to macrophages, IL-1 mRNA was clearly induced. Induction of the IL-1 alpha gene seemed to require the recognition of class II MHC products on the macrophage because of the following observations: specific rather than third-party macrophages were responsive to the T blast but not to T cell-conditioned media; induction was blocked by an anti-Ia mAb; CD4+ rather than CD8+ blasts were active; and polyclonal Con A blasts were much less efficient than antigen-specific T cells. Our data indicate that the strongest signal for IL-1 production during the macrophage-T cell interaction occurs in the efferent limb of the response, after rather than before the formation of class II MHC-restricted T lymphoblasts.

scholarly journals Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line.

1984 ◽  
Vol 159 (6) ◽  
pp. 1637-1652 ◽  
Author(s):  
G Scala ◽  
Y D Kuang ◽  
R E Hall ◽  
A V Muchmore ◽  
J J Oppenheim
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Function ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Inhibitory Factor ◽  
Accessory Cell ◽  
Con A ◽  
Human B Cell

In the present paper we report that the ROHA -9 cell line, an Epstein-Barr virus (EBV)-transformed human B cell line with accessory cell capabilities, constitutively secretes a soluble factor with the biochemical and biological characteristics of human monocyte-derived IL-1. The IL-1 derived from ROHA -9 augmented murine thymocyte proliferation and enhanced the proliferative response of human T lymphocytes to concanavalin A (Con A). The ROHA -9-derived IL-1 activity eluted from Sephacryl S-200 in two peaks, at 15- 18K and 32- 35K mol wt, eluted from DEAE-Sephacel at 50-80 and 110-130 mM NaCl, and showed charge heterogeneity with peaks at pI 7.3, 6.1, and 4.1 on isoelectrofocusing (IEF). These findings suggest that B cells may elaborate an IL-1-like activity. During the logarithmic growth of ROHA -9 cells, a inhibitory factor that inhibited the response of mouse thymocytes to IL-1 was also produced. This factor had a mol wt of 95K on Sephacryl S-200, eluted at 150 mM NaCl on DEAE-Sephacel and showed a peak of pI 4.7 on preparative IEF. The inhibitory factor appeared to be selective in its effects on IL-1 responses, since it did not inhibit the activity of IL-2 on mouse thymocytes or on the growth of the IL-2-dependent CT6 cell line. This "contra-IL-1" inhibited the response of murine thymocytes to suboptimal (1 microgram/ml) but not optimal (10 micrograms/ml) doses of Con A and the response of human peripheral blood lymphocytes to streptolysin O ( SLO ) or to alloantigens. Moreover, the factor could be absorbed by mouse thymocytes but not by CT6 cells, and such thymocytes pretreated with contra-IL-1 failed to response to IL-1. Although this inhibitor is the product of a transformed B cell line, it may be representative of regulatory substances that normally control IL-1 activities either at the extracellular or intracellular level.

scholarly journals Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes.

1978 ◽  
Vol 148 (2) ◽  
pp. 393-407 ◽  
Author(s):  
J Mauel ◽  
Y Buchmüller ◽  
R Behin
Keyword(s):  
Macrophage Activation ◽  
Protozoan Parasite ◽  
Peritoneal Macrophages ◽  
Mixed Lymphocyte Culture ◽  
Culture Conditions ◽  
Lymphocyte Culture ◽  
Con A ◽  
Infected Cells ◽  
Spleen Lymphocytes ◽  
Leishmania Enriettii

When cultures of normal mouse peritoneal macrophages were infected with the intracellular protozoan parasite Leishmania enrietti, the micro-organism was found to survive intracellularly for several days, apparently without multiplication. However, exposure of infected macrophages to certain stimuli led to rapid parasite killing and digestion, providing a sensitive assay with which the mechanisms of macrophage activation can be studied. Microbicidal activity was induced by incubation of macrophages with syngeneic spleen lymphocytes, which were stimulated either by allogeneic cells in mixed lymphocyte culture (MLC) or by the plant lectin concanavalin A (Con A). Cocultivation with MLCs led to parasite killing within 48-72 h, whereas exposure of infected cells to Con A-stimulated lymphocytes resulted in substantial destruction of the micro-organism within less than 24 h, an effect which was dependent on the presence of thymus-derived lymphocytes and was inhibited by alpha methyl-mannoside. Incubation with Con A-stimulated lymphocytes also led to lysis of part of the macrophage monolayer. However, parasite killing did not result from decreased macrophage survival, as destruction of the micro-organism was highest under culture conditions which were the least detrimental to the phagocytes. Conversely, excess numbers of Con A-stimulated lymphocytes were less efficient at inducing macrophage activation and displayed marked toxicity to the macrophage monolayer. When spleen cells were stimulated by Con A at concentrations above 10 mug/ml, a decrease was noted in the capacity of macrophages to destroy the parasite, probably reflecting a toxicity of the lectin for lymphocytes resulting in impaired activating capacity.

Accessory cell function in a Con A response: Role of Ia and interleukin 1

1987 ◽  
Vol 106 (2) ◽  
pp. 250-259 ◽  
Author(s):  
Keizo Kohno ◽  
Terutaka Kakiuchi ◽  
Makoto Takeuchi ◽  
Sumiko Taira ◽  
Hideo Nariuchi
Keyword(s):  
Cell Function ◽  
Interleukin 1 ◽  
Accessory Cell ◽  
Con A
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