Increase in plasmacytoid and myeloid dendritic cells by progenipoietin-1, a chimeric Flt-3 and G-CSF receptor agonist, in SIV-Infected rhesus macaques.
As in HIV-1 infection in humans, SIVsm infection of rhesus macaques causes a slow progressive loss of CD4 T-cells followed by the onset of AIDS. In addition, there is a loss of dendritic cells (DC) in peripheral blood, peripheral lymphoid tissues, and the skin. Increasing the number of CD4 T cells and DC may be an important step in restoring immune competence and thus delay disease progression. Recently, progenipoietins (ProGP), a new family of chimeric Flt3 and G-CSF receptor agonists, were demonstrated to possess the capacity to mobilize hematopoietic progenitor cells in normal rhesus monkeys. In addition, these molecules induced increased numbers of myeloid cells, including dendritic cells, in the blood. Here we demonstrate that SIVsm-infected macaques, treated with ProGP-1, developed increased numbers of both plasmacytoid (CD123+, CD11c-) and myeloid (both CD11b+, CD11c+, and CD123-, CD11c+ subsets) DC and CD4 and CD8 T cells in peripheral blood. Importantly, during treatment, no changes in plasma virus load were observed. After 14 to 20 days of treatment, antibodies were formed against ProGP in all animals. As a consequence, white blood cell levels returned to baseline in several animals. In other animals values only returned to baseline after termination of ProGP treatment. In conclusion, ProGP-1 may be used to generate a transient increase in DC as well as CD4 T-cell numbers, thereby creating a window of opportunity for immunotherapeutic intervention.
Koopman
Gerrit
G
BPRC, Rijswijk, The Netherlands. koopman@bprc.nl
Niphuis
Henk
H
Haaksma
Anton G M
AG
Farese
Ann M
AM
Casey
Dan B
DB
Kahn
Larry E
LE
Mann
Dean
D
MacVittie
Thomas J
TJ
Woulfe
Susan L
SL
Heeney
Jonathan L
JL
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D011518:Proto-Oncogene Proteins / Q000819:agonists*; D012367:RNA, Viral / Q000097:blood; D020794:Receptor Protein-Tyrosine Kinases; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000819:agonists*; D011994:Recombinant Proteins; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D051941:fms-Like Tyrosine Kinase 3
D000906:Antibodies; D015703:Antigens, CD; D003115:Colony-Stimulating Factors; D011518:Proto-Oncogene Proteins; D012367:RNA, Viral; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; C434603:progenipoietin-1; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3