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.
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Authors | R Keith Reeves, Qing Wei, Jackie Stallworth, Patricia N Fultz |
Journal | AIDS research and human retroviruses
(AIDS Res Hum Retroviruses)
Vol. 25
Issue 12
Pg. 1313-28
(Dec 2009)
ISSN: 1931-8405 [Electronic] United States |
PMID | 20001520
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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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
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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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