Interleukin-10 produced by the innate immune system masks in vitro evidence of acquired T-cell immunity to E. coli.

• Bacteria trigger stimulation of antigen-specific, as well as innate, immune responses. Cytokines and other products of cells belonging to the innate immune system may interfere with the detection of acquired immunity to whole bacteria in vitro. Proliferation and cytokine production by human blood mononuclear cells in response to a whole UV-killed Escherichia coli was compared with the response to commonly used antigen preparations: purified protein derivative (PPD), Candida albicans and influenza proteins. E. coli induced a weaker proliferative response with later onset than did the other antigens, and production of interferon (IFN)-gamma comparable with that in response to C. albicans and influenza vaccine, but lower than that induced by PPD. Both proliferation and IFN-gamma production were abolished by removal of CD4 cells or blocking of HLA-D, but not CD1 antigen-presenting molecules. Purified lipopolysaccharide (LPS) induced neither proliferation nor IFN-gamma production. None of the antigen preparations stimulated interleukin (IL)-4 production but, in contrast to the other antigens, whole E. coli, as well as purified O6 LPS, induced large quantities of IL-10. IL-10 production was independent of CD4 cells or HLA-D molecules. Blocking of IL-10 by neutralizing antibodies increased both E. coli-induced proliferation and IFN-gamma production markedly. Conversely, the addition of whole E. coli or LPS to cultures stimulated with other antigens (C. albicans or Staphylococcus aureus) down-regulated proliferative and IFN-gamma responses, an effect which was at least partly IL-10 dependent. The results indicate a substantial T-cell memory to commensal E. coli, but suggest that the evidence of such memory, e.g. proliferation and IFN-gamma production, is effectively prevented by IL-10 and perhaps other factors produced by monocytes in response to bacteria. Thus, the innate immune responses must be taken into account when acquired immune responses to microbes are measured.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Antigens

CD1

physiology

Escherichia coli

immunology

Humans

Immunity

Interferon-gamma

biosynthesis

Interleukin-10

biosynthesis

Lipopolysaccharides

pharmacology

Lymphocyte Activation

drug effects

T-Lymphocytes

immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)