关键词: CD8(+) T cells HIV HIV/SIV suppression SIV T cell memory antiviral function cytotoxic T cells elite controllers natural control pathogenesis

Mesh : Animals CD4-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / immunology Cell Proliferation Chronic Disease Haplotypes / genetics Immunologic Memory Lymph Nodes / pathology Lymphocyte Count Macaca fascicularis Major Histocompatibility Complex Simian Acquired Immunodeficiency Syndrome / blood immunology virology Simian Immunodeficiency Virus / immunology Viremia

来  源:   DOI:10.1016/j.celrep.2020.108174   PDF(Sci-hub)

Abstract:
Highly efficient CD8+ T cells are associated with natural HIV control, but it has remained unclear how these cells are generated and maintained. We have used a macaque model of spontaneous SIVmac251 control to monitor the development of efficient CD8+ T cell responses. Our results show that SIV-specific CD8+ T cells emerge during primary infection in all animals. The ability of CD8+ T cells to suppress SIV is suboptimal in the acute phase but increases progressively in controller macaques before the establishment of sustained low-level viremia. Controller macaques develop optimal memory-like SIV-specific CD8+ T cells early after infection. In contrast, a persistently skewed differentiation phenotype characterizes memory SIV-specific CD8+ T cells in non-controller macaques. Accordingly, the phenotype of SIV-specific CD8+ T cells defined early after infection appears to favor the development of protective immunity in controllers, whereas SIV-specific CD8+ T cells in non-controllers fail to gain antiviral potency, feasibly as a consequence of early defects imprinted in the memory pool.
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