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Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques.

Abstract
Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Furthermore, it was recently demonstrated that a sustained loss of mDCs and pDCs occurs in SIV-infected macaques. Since loss of functional DC populations might impair innate immune responses to opportunistic microorganisms and neoplastic cells, we explored whether inoculation of naive and SIV- or SHIV-infected pigtailed macaques with the hematopoietic cytokine FLT3-ligand (FLT3-L) would expand the number of mDCs and pDCs in vivo. After the macaques received supraphysiologic doses of FLT3-L, mDCs, pDCs, and monocytes increased up to 45-fold in blood, lymph nodes, and bone marrow (BM), with DC expansion in the BM preceding mobilization in blood and lymphoid tissues. FLT3-L also increased serum levels of IL-12, at least transiently, and elicited higher surface expression of HLA-DR and the activation markers CD25 and CD69 on NK and T cells. During and after treatment of infected animals, APCs increased in number and were activated; however, CD4(+) T cell numbers, virion RNA, and anti-SIV/SHIV antibody titers remained relatively stable, suggesting that FLT3-L might be a safe modality to expand DC populations and provide therapeutic benefit during chronic lentivirus infections.
AuthorsR Keith Reeves, Qing Wei, Jackie Stallworth, Patricia N Fultz
JournalAIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 25 Issue 12 Pg. 1313-28 (Dec 2009) ISSN: 1931-8405 [Electronic] United States
PMID20001520 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • CD69 antigen
  • Interferon-alpha
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • flt3 ligand protein
  • Interleukin-12
Topics
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Antigens, CD (drug effects, metabolism)
  • Antigens, Differentiation, T-Lymphocyte (drug effects, metabolism)
  • B7-1 Antigen (drug effects, metabolism)
  • B7-2 Antigen (drug effects, metabolism)
  • CD4-Positive T-Lymphocytes (drug effects, immunology)
  • CD40 Antigens (agonists, metabolism)
  • CD8-Positive T-Lymphocytes (drug effects, immunology)
  • Dendritic Cells (drug effects, immunology)
  • Female
  • Interferon-alpha (blood)
  • Interleukin-12 (agonists, blood)
  • Interleukin-2 Receptor alpha Subunit (drug effects, metabolism)
  • Killer Cells, Natural (drug effects, immunology)
  • Lectins, C-Type (drug effects, metabolism)
  • Macaca nemestrina
  • Male
  • Membrane Proteins (administration & dosage)
  • Simian Acquired Immunodeficiency Syndrome (immunology)
  • Simian Immunodeficiency Virus
  • Tumor Necrosis Factor-alpha (blood)

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