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

Abstract

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.

Comparison of the Accessory Activity of Murine Peritoneal Cavity Macrophage Derived Dendritic Cells and Peritoneal Cavity Macrophages in a Mixed Lymphocyte Reaction.

“…In contrast, other studies have shown that macrophages can increase the sensitivity of MLR to Peyer's patch cells [27]. It is most likely that this effect may be mediated by macrophages production of IL-1 which is not produced by DC [16], but which amplifies DC function [15] and all these factors require further experimental analysis. Although it has been reported in previous studies that an allogeneic MLR can occur without the involvement of IL-1 [23], it is likely that all T cell responses require a number of co-stimulatory factors [11].…”

Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to IntactStreptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

“…Although IL-1 has been shown to have a direct costimulatory effect on B cells (6), the data on TI responses appear to indicate that this property is not critical in vivo. The role of IL-1 in TD responses could reflect its ability to directly costimulate T cells (5), as well as indirectly through costimulation of Ag-presenting DC (7). The ability of IL-1 to costimulate chemokine release (53,54) may also help to promote TD immunity.…”

“…IL-1 plays a key role in mediating innate host protection in response to pathogens, but is also a major inducer of tissue damage during infections and in pathologic conditions such as asthma and various autoimmune diseases (3,4). IL-1 also exerts effects on cells involved in the adaptive immune response, acting directly as a costimulus for T cells (5), B cells (6), and dendritic cells (DCs) 4 (7). In this regard, exogenous IL-1 can act as an adjuvant to enhance Ab production to particulate (8) and soluble protein (9) Ags.…”

Signaling Lymphocytic Activation Molecule Is Expressed on Mature CD83+ Dendritic Cells and Is Up-Regulated by IL-1β

“…Koide et al (31) reported that IL-1 enhances the clustering and T cell stimulatory capacity of spleen DC. Heufler et al (32) found that IL-1 enhances the stimulatory capacity of murine Langerhans cells matured in the presence of GM-CSF.…”