Low molecular thymic peptides stimulate human blood dendritic cells.
Dendritic cells are considered to be the most potent antigen-presenting cells and are thus promising new tools for the immunotherapy of cancer. They respond to various stimuli by differentiation (expression of CD83) and up-regulation of costimulatory surface molecules. Thymic peptides have immunostimulatory and immunomodulating properties. Their therapeutic potential in immunotherapy of cancer has been discussed. To test whether thymic peptides act on dendritic cells, we examined the effects of a standardized thymic peptide preparation on cultured human monocyte-derived dendritic cells. Addition of thymic peptides resulted in enhanced expression of the specific differentiation marker CD83 in a dose dependent manner. Moreover, thymic peptides induced the up-regulation of costimulatory molecules including CD86, CD80, HLA-DR and HLA-ABC. After priming with thymic peptides dendritic cells showed an enhanced expression of IL-8 and TNF-alpha mRNA and protein release. Dendritic cells stimulated with thymic peptides were able to induce proliferation of autologous T cells as measured by 3H-thymidine incorporation in mixed Lymphocyte reaction. In combination with a low dosage of keyhole limpet hemocyanin, thymic peptides showed additive effects in the up-regulation of CD83 and costimulatory surface markers. Our findings indicate that thymic peptides per se act on professional antigen-presenting cells in a stimulatory manner and were presented by these cells. Furthermore, thymic peptides enhance the response of dendritic cells to low dosages of a standard nominal antigen. Therefore, thymic peptides could improve the immunological activity especially against low amounts of endogenous antigens.
Mayer
G
G
Strathmann Research GmbH, Hamburg, Germany.
Pohlmeyer
K
K
Caliebe
A
A
Heimueller
E
E
Behnke
B
B
Steimann
G
G
Lange
C
C
Beuth
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000378:metabolism; D006241:Haptens / Q000494:pharmacology; D006433:Hemocyanins / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000502:physiology*; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D006241:Haptens; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin