title: Elevated granzyme B+B-cell level in SIV-infection correlate with viral load and low CD4 T-cell count.
abstract: Granzyme B-expressing (GrB+) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB+B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts. When investigating GrB+B cells in different compartments, levels were highest in blood, spleen and bone marrow, but considerably lower in lymph nodes and tonsils. Analysis of expression of various surface markers on this particular B-cell subset in SIV-infected macaques revealed differences between the phenotype in macaques and in humans. GrB+B cells in SIV-infected rhesus macaques exhibit an elevated expression of CD5, CD10, CD25 and CD27, while expression of CD19, CD185 and HLA-DR is reduced. In contrast to human GrB+B cells, we did not observe a significantly increased expression of CD43 and CD86. B-cell receptor stimulation in combination with IL-21 of purified B cells from healthy animals led to the induction of GrB expression. Furthermore, initial functional analyses indicated a regulatory role on T-cell proliferation. Overall, our data pave the way for longitudinal analyses including studies on the functionality of GrB+B cells in the nonhuman primate model for AIDS.
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.|Department of Virology Research, Animal Health Research Institute, Agriculture Research Center, Giza, Egypt.|Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
authors: Ahmad
authors: A
authors: Kotb
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
authors: Antonina
authors: A
authors: Klippert
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
authors: Maria
authors: M
authors: Daskalaki
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
authors: Ulrike
authors: U
authors: Sauermann
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
authors: Christiane
authors: C
authors: Stahl-Hennig
authors: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
authors: Berit
authors: B
authors: Neumann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D019562:Viral Load / Q000276:immunology*
chemical_list: D016753:Interleukin-10; D053804:Granzymes