Spontaneous proliferation and type 2 cytokine secretion by CD4+T cells in patients with metastatic melanoma vaccinated with antigen-pulsed dendritic cells.
We observed the induction of spontaneous, i.e., without adding exogenous antigen, in vitro proliferation of PBMCs from patients with stage IV melanoma who underwent repeated vaccinations with antigen-loaded dendritic cells (DCs) derived from CD34(+) hematopoietic progenitors (CD34-DCs). Proliferating cells are CD4(+)T cells. Their proliferation is dependent on (1) CD11c(+) myeloid DCs, since their depletion from PBMCs abolishes it; and (2) IL-2, as it can be blocked by neutralizing anti-IL-2 antibodies. Spontaneous proliferation is associated to the secretion of type 2 cytokines. To analyze the frequency of spontaneous proliferation induction in the cohort of 18 vaccinated patients, an index of spontaneous proliferation was defined as a ratio of PBMCs proliferation from post- vs pre-DC vaccination blood samples. Ten out of sixteen analyzed patients showed an index > 2. The index of spontaneous proliferation correlates with antigen-specific PBMC proliferation to the vaccine antigen KLH. Furthermore, both spontaneous- and antigen-specific proliferation in PBMC cultures are dependent on blood myeloid DCs.
Palucka
A Karolina
AK
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204, USA. karolinp@baylorhealth.edu
Connolly
John
J
Ueno
Hideki
H
Kohl
John
J
Paczesny
Sophie
S
Dhodapkar
Madhav
M
Fay
Joseph
J
Banchereau
Jacques
J
D017951:Antigen Presentation; D039521:CD11c Antigen; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D006433:Hemocyanins / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D009362:Neoplasm Metastasis
D039521:CD11c Antigen; D016207:Cytokines; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin