Indirect IL-4 pathway in type 1 immunity.
Recall Ag-specific IL-4 was detected in the spleen and in the blood, but not in lymph nodes of mice in which polarized type 1 immunity was induced. This IL-4 was not produced by T cells, but soluble factors secreted by the recall Ag-activated T cells, including IL-3, triggered cells of the innate immune system, primarily mast cells, to secrete IL-4. This notion has profound implications for immunodiagnostics: the detection of apparently recall Ag-specific IL-4 does not necessarily reflect the presence of Th2 or Th0 memory T cells with long-term cytokine commitment as is of interest for assessing adoptive immunity. We found that in vivo the indirect IL-4 pathway did not suffice to trigger IgE isotype switching, but promoted IgG1 production and inhibited type 1 T cell differentiation. Therefore, the indirect IL-4 pathway can explain partial type 2 immune response phenotypes in vivo in face of unipolar Th1 T cell immunity. The representation of mast cells in different tissues may explain why immune responses in certain organs are more type 2 biased. Therefore, the indirect pathway of IL-4 production represents a novel type of interaction between the innate and the adoptive immune system that can contribute to the outcome of host defense and immune pathology.
Karulin
Alexey Y
AY
Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Hesse
Maike D
MD
Yip
Hualin C
HC
Lehmann
Paul V
PV
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D007111:Immunity, Cellular / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D007377:Interleukin-3; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D005620:Freund's Adjuvant