IL-10 regulates early IL-12-mediated immune responses induced by the radiation-attenuated schistosome vaccine.

Abstract

Radiation-attenuated (RA) schistosomes penetrate the host via the skin where they stimulate intense inflammatory reactions and the release of pro-inflammatory IL-12, important for T(h)1-type immune responses which are partially host protective. However, RA larvae also induce the secretion of regulatory IL-10. We now show that following vaccination of IL-12p40(-/-) mice, abundant IL-10 was produced by in vitro cultured skin biopsies between days 4 and 14, corresponding to the down-regulation of MHC II expression by cells in the dermis and cells that emigrate from the skin. In IL-10(-/-) mice, inflammation of the vaccination site was increased with larger numbers of IL-12p40(+), MHC II(+) and CD86(+) cells in the dermal exudate, and was associated with elevated levels of skin-derived IL-12p40 and IL-1beta. These changes in IL-10(-/-) mice were also reflected by an increased number of cells in the skin-draining lymph nodes (sdLN) and greater levels of lymphocyte proliferation. Moreover, such mice had increased numbers of CD4(+) sdLN cells that were CD25(+), CD28(+) or CD152(+) and accessory cells that were CD40(+) or MHC II(+). Finally, the secretion of IFN-gamma (and IL-12p40) by in vitro cultured sdLN cells was substantially raised in IL-10(-/-) mice, but much reduced in IL-12p40(-/-) mice, resulting in the development of highly polarized T(h)1 and T(h)2 cytokine profiles in the two groups of mice respectively. We conclude that IL-10 has an important role early in the regulation of IL-12-mediated priming of acquired immune responses, and effectively contains excessive dermal inflammation and prevents the development of highly polarized T(h)1-type responses.

• Authors: Karen G Hogg, Supeecha Kumkate, Adrian P Mountford
• Journal: International immunology (Int Immunol) Vol. 15 Issue 12 Pg. 1451-9 (Dec 2003) ISSN: 0953-8178 [Print] England
• PMID: 14645154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Antigens, CD
• B7-2 Antigen
• CD4 Antigens
• Cd86 protein, mouse
• Histocompatibility Antigens Class II
• Interleukin-1
• Interleukin-12 Subunit p40
• Interleukin-18
• Membrane Glycoproteins
• Protein Subunits
• Vaccines, Attenuated
• Interleukin-10
• Interleukin-12
• Interleukin-4
• Interferon-gamma
• Leukocyte Common Antigens

Topics

• Animals
• Antigens (pharmacology)
• Antigens, CD (metabolism)
• B7-2 Antigen
• CD4 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (metabolism)
• Cell Count
• Cell Division (drug effects)
• Cells, Cultured
• Culture Techniques
• Ear, External (immunology, pathology)
• Female
• Flow Cytometry
• Histocompatibility Antigens Class II (metabolism)
• Immunohistochemistry
• Inflammation (immunology)
• Injections, Intradermal
• Interferon-gamma (metabolism)
• Interleukin-1 (metabolism)
• Interleukin-10 (genetics, immunology, physiology)
• Interleukin-12 (genetics, immunology, physiology)
• Interleukin-12 Subunit p40
• Interleukin-18 (metabolism)
• Interleukin-4 (metabolism)
• Leukocyte Common Antigens (metabolism)
• Lymph Nodes (cytology)
• Lymphocyte Activation (physiology)
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Protein Subunits (genetics, immunology, physiology)
• Schistosoma mansoni (immunology, radiation effects)
• Skin (chemistry, immunology, pathology)
• Th1 Cells (immunology, physiology)
• Th2 Cells (immunology, physiology)
• Vaccination
• Vaccines, Attenuated (immunology)