Low molecular thymic peptides stimulate human blood dendritic cells

Dendritic cells are considered to be the most potent antigen-presenting cel ls and ale thus promising new tools for the immunotherapy of cancer: They r espond to various stimuli by differentiation (expression of CD83) and lip-r egulation of costimulatory surface molecules. Thymic peptides have immunost imulatory and immunomodulating properties. Their therapeutic potential in i mmunotherapy of cancel has been discussed. To test whether thymic peptides act on dendritic cells, we examined the effects of a standardized thymic pe ptide preparation on cultured human monocyte-derived dendritic cells. Addit ion of thymic peptides resulted in enhanced expression of the specific diff erentiation marker CD83 in a dose dependent manner: Moreover; thymic peptid es induced the up-regulation of costimulatory molecules including CD86, CD8 0, HLA-DR and HLA-ABC. After priming with thymic peptides dendritic cells s howed an enhanced expression of IL-8 and TNF-alpha mRNA and protein release . Dendritic cells stimulated with thymic peptides were able to induce proli feration of autologous T cells as measured by H-3-thymidine incorporation i n mired Iymphocyte reaction. In combination with a low dosage of keyhole li mpet hemocyanin, thymic peptides showed additive effects in the upregulatio n of CD83 and costimulatory surface markers. Our findings indicate that thy mic peptides per se act on professional antigen- presenting cells in a stim ulatory manner and were presented by these cells. Furthermore, thymic pepti des enhance the response of dendritic cells to low dosages of a standard no minal antigen. Therefore, thymic peptides could improve the immunological a ctivity especially against low amounts of endogenous antigens.