IFN-gamma receptor signaling regulates memory CD8+ T cell differentiation.

Abstract

IFN-gamma regulates multiple processes in the immune system. Although its antimicrobial effector functions are well described, less is known about the mechanisms by which IFN-gamma regulates CD8(+) T cell homeostasis. With the help of adoptive T cell transfers, we show in this study that IFN-gammaR signaling in CD8(+) T cells is dispensable for expansion, contraction, and memory differentiation in response to peptide vaccination. In contrast, host IFN-gammaR signaling counterregulates CD8(+) T cell responses and the generation of effector memory T cell processes, which are partially regulated by CD11b(+) cells. Similar to vaccination-induced proliferation, host IFN-gammaR signaling limits the expansion of naive CD8(+) T cells and their differentiation into effector memory-like T cells in lymphopenic mice. In contrast to peptide vaccination, IFN-gammaR signaling in CD8(+) T cells contributes to memory fate decision in response to lymphopenia, an effect that is fully reversed by high-affinity TCR ligands. In conclusion, we show that host IFN-gammaR signaling controls the magnitude of CD8(+) T cell responses and subsequent memory differentiation under lymphopenic and nonlymphopenic conditions. In contrast, IFN-gammaR signaling in CD8(+) T cells does not affect cell numbers under either condition, but it directs memory fate decision in response to weak TCR ligands.

• Authors: Ozen Sercan, Diana Stoycheva, Günter J Hämmerling, Bernd Arnold, Thomas Schüler
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 6 Pg. 2855-62 (Mar 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20164422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Lipopolysaccharides
• OVA-8
• Peptide Fragments
• Receptors, Interferon
• Interferon-gamma
• Ovalbumin

Topics

• Adoptive Transfer
• Animals
• CD8-Positive T-Lymphocytes (cytology, immunology, metabolism, transplantation)
• Cell Differentiation (genetics, immunology)
• Cell Proliferation
• Cells, Cultured
• Chickens
• Coculture Techniques
• Immunization
• Immunologic Memory
• Interferon-gamma (deficiency, genetics, metabolism)
• Ligands
• Lipopolysaccharides (administration & dosage, immunology)
• Lymphopenia (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Ovalbumin (administration & dosage, immunology)
• Peptide Fragments (administration & dosage, immunology)
• Receptors, Interferon (deficiency, genetics, physiology)
• Signal Transduction (genetics, immunology)
• Interferon gamma Receptor