Lipid A directly inhibits IL-4 production by murine Th2 cells but does not inhibit IFN-γ production by Th1 cells

Abstract

Lipopolysaccharide (LPS) is known to be an immunopotentiator but its effect on cytokine production by Th1 and Th2 cells is unknown. We found that high amounts of LPS, its lipid A moiety, and a lipid A analog all induced a decrease in IL-4 production and an increase in IFN-gamma production when given to keyhole limpet hemocyanin (KLH)-restimulated lymph node cells prepared from KLH-primed mice. Lipid A was similarly found to inhibit IL-4 production by purified CD4+ T cells and Th2 clones activated with immobilized anti-CD3epsilon and anti-CD28 antibodies, suggesting that the inhibition is not indirectly mediated through effects on antigen-presenting cells. No inhibitory effect of lipid A was observed on IFN-gamma production by a Th1 clone. Production of both IL-4 by the Th2 clones and IFN-gamma by the Th1 clone were inhibited by the immunosuppressive agent cyclosporin A. These findings indicate that lipid A can directly inhibit IL-4 production by CD4+ T cells without inhibiting the production of IFN-gamma. Lipid A may therefore become a useful tool to study the intracellular events that differentiate Th1 and Th2 cells.

Role of anti-CD3 in modulation of Th1-type immune response in Shigella dysenteriae infection

“…In parallel, a high level of CD25 (IL2R) expression until day 28 in challenged groups after successful immunization was considered as a generalized T-cell activation with increased antibody response. As a result, increased IL2R sharing with IL2 to form a high affinity receptor complex promotes cell proliferation for CD4 þ T-cells through cytokine-specific signals (Watanabe et al, 1999;Taniguchi & Minami, 1993). Consistent with the previous study, anti-CD3-antibody-stimulated T-cells induced Th1 type cyto- kines (IL2) produced by naïve T-cells in the murine or human system (Fang et al, 2000;Jenkins et al, 1990).…”

“Dirty little secrets”—Endotoxin contamination of recombinant proteins

“…Dendritic cells and macrophages are especially noted for their response to bacterial TLR agonists. However, there is also a growing body of evidence to suggest T cells also express a number of TLRs [39][40][41][42][43] and, furthermore, that they can respond directly to TLR agonists [39,40,[44][45][46]. Given that a number of cell types can respond to TLR agonists, these observations ensure that caution must be exercised not only in cell culture systems containing pure cultures of TLR-expressing cells but also in other cell culture systems where contamination with such endotoxin-responsive cells may be an issue.…”