Primary human immunodeficiency virus type 1-specific CD8+ T-cell responses induced by myeloid dendritic cells.
Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (HIV-1). Here we show that a primary CD8(+) T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34(+) stem cells of neonatal cord blood. Optimal priming of single-cell gamma interferon (IFN-gamma) production by CD8(+) T cells required CD4(+) T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8(+) T-cell responses, defined as single-cell production of more than one cytokine (IFN-gamma, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1beta), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8(+) T-cell responses to HIV-1 and other viral antigens.
Graduate School of Public Health1 and School of Medicine,2 University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Bonnie A
BA
Colleton
Xiao-Li
XL
Huang
Nada M
NM
Melhem
Zheng
Z
Fan
Luann
L
Borowski
Giovanna
G
Rappocciolo
Charles R
CR
Rinaldo
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007231:Infant, Newborn; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology
D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen