Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques.
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.
Reeves
R Keith
RK
Department of Microbiology, University of Alabama at Birmingham (UAB), Birmingham, Alabama 35294, USA.
Wei
Qing
Q
Stallworth
Jackie
J
Fultz
Patricia N
PN
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000378:metabolism; D018122:B7-1 Antigen / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen / Q000187:drug effects / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000819:agonists / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016898:Interferon-alpha / Q000097:blood; D018664:Interleukin-12 / Q000819:agonists / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000187:drug effects / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037181:Lectins, C-Type / Q000187:drug effects / Q000378:metabolism; D008254:Macaca nemestrina; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016898:Interferon-alpha; D018664:Interleukin-12; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C084881:flt3 ligand protein