IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients.
IL-15 is a critical cytokine for the maintenance of memory-phenotype CD8 cells in mice. Here, we investigated the role of IL-15 in the neurological disease termed human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The high number of viral-specific CD8 cells in these patients is associated with inflammatory responses in the central nervous system. Because IL-15 is overexpressed in these patients, we asked whether IL-15 contributes to the persistence of human T cell lymphotropic virus I viral-specific CD8 cells. Using ex vivo cultures of HAM/TSP peripheral blood mononuclear cells, we demonstrated that in the majority of patients examined here blocking IL-15 action resulted in a decrease in the number of viral-specific CD8 cells. This decrease was caused by both inhibition of proliferation and induction of apoptosis in these cells. The data indicate that IL-15 plays a major role in the maintenance of viral-specific CD8 cells in HAM/TSP.
Azimi
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N
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1374, USA. nazli@helix.nih.gov
Nagai
M
M
Jacobson
S
S
Waldmann
T A
TA
D019138:Antibodies, Blocking / Q000494:pharmacology; D000956:Antigens, Viral; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D016356:Gene Products, tax / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism
D019138:Antibodies, Blocking; D000956:Antigens, Viral; D016356:Gene Products, tax; C508024:IL15RA protein, human; D019409:Interleukin-15; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2