IFN-gamma expressed by T cells regulates the persistence of antigen presentation by limiting the survival of dendritic cells.
Ag presentation to T cells orchestrates the development of acquired immune response. Although it is considered that Ag presentation may persist at high levels during chronic infections, we have previously reported that in mice infected with bacillus Calmette-Guérin, Ag presentation gets drastically curtailed during the chronic stage of infection despite antigenic persistence. In this report we evaluated the mechanism of this curtailment. Ag presentation declined precipitously as the T cell response developed, and Ag presentation was not curtailed in mice that were deficient in CD8(+) T cells or MHC class II, suggesting that T cells regulate Ag presentation. Curtailment of Ag presentation was reduced in IFN-gamma-deficient mice, but not in mice with a deficiency/mutation in inducible NOS2, perforin, or Fas ligand. In hosts with no T cells (Rag1(-/-)), Ag presentation was not curtailed during the chronic stage of infection. However, adoptive transfer of wild-type, but not IFN-gamma(-/-), CD4(+) and CD8(+) T cells into Rag1-deficient hosts strongly curtailed Ag presentation. Increased persistence of Ag presentation in IFN-gamma-deficient hosts correlated to increased survival of dendritic cells, but not of macrophages, and was not due to increased stimulatory capacity of IFN-gamma-deficient dendritic cells. These results reveal a novel mechanism indicating how IFN-gamma prevents the persistence of Ag presentation, thereby preventing memory T cells from going into exhaustion.
Russell
Marsha S
MS
National Research Council Institute for Biological Sciences, University of Ottawa, Ottawa, Ontario, Canada.
Dudani
Renu
R
Krishnan
Lakshmi
L
Sad
Subash
S
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007156:Immunologic Memory / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
D006131:Growth Inhibitors; D007371:Interferon-gamma