Pathogen-specific CD8 T cell responses are directly inhibited by IL-10.
Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 is a regulatory cytokine that can restrict T cell responses by inhibiting APC functions. IL-10, however, can also have direct effects on T cells. Although blockade or genetic deletion of IL-10 enhances T cell-mediated resistance to infections, the extent to which IL-10 limits in vivo APC function or T cell activation/proliferation remains unknown. Herein, we demonstrate that primary and memory CD8 T cell responses following Listeria monocytogenes infection are enhanced by the absence of IL-10. Surface expression of the IL-10R is transiently up-regulated on CD8 T cells following activation, suggesting that activated T cells can respond to IL-10 directly. Consistent with this notion, CD8 T cells lacking IL-10R2 underwent greater expansion than wild-type T cells upon L. monocytogenes infection. The absence of IL-10R2 on APCs, in contrast, did not enhance T cell responses following infection. Our studies demonstrate that IL-10 produced during bacterial infection directly limits expansion of pathogen-specific CD8 T cells and reveal an extrinsic regulatory mechanism that modulates the magnitude of memory T cell responses.
Biswas
Partha Sarathi
PS
Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Pedicord
Virginia
V
Ploss
Alexander
A
Menet
Ewa
E
Leiner
Ingrid
I
Pamer
Eric G
EG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053701:Receptors, Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D053701:Receptors, Interleukin-10; D016753:Interleukin-10