Paucity of functional T-cell memory to melanoma antigens in healthy donors and melanoma patients Journal Article
| Authors: | Dhodapkar, M. V.; Young, J. W.; Chapman, P. B.; Cox, W. I.; Fonteneau, J. F.; Amigorena, S.; Houghton, A. N.; Steinman, R. M.; Bhardwaj, N. |
| Article Title: | Paucity of functional T-cell memory to melanoma antigens in healthy donors and melanoma patients |
| Abstract: | The functional characteristics of CD8+ T cells specific for melanoma antigens (MAs) have often been defined after in vitro culture using nonprofessional antigen-presenting cells. We have examined CD8+ T-cell immunity to MAs and a viral antigen (influenza) in uncultured T cells of healthy donors and melanoma patients using autologous, mature, monocyte-derived dendritic cells (DCs) pulsed with peptide antigens and viral vectors. Antigen-specific IFN-gamma -producing T cells reactive with HLA-A*0201-restricted peptides from four melanoma antigens (MelanA/MART-1, MAGE-3, tyrosinase, and gp100) were detected only at low frequencies (<30 per 2 x 10(5) peripheral blood mononuclear cells for each of the Mils) from HLA-A2.1-positive healthy donors (n = 12) and patients with stages III/IV melanoma (n = 8), Detection of MA-specific, but not influenza matrix peptide (Flu-MP)-specific, T cells required a high concentration (10 <mu>g/ml) of the peptide in this assay. Furthermore, these T cells did not recognize endogenously processed antigen on tumor cell lines or cells infected with viral vectors capable of expressing MAs, The use of autologous, mature DCs led to a significant. increase in the number of Flu-MP, but not MA-specific, T cells in 16-h ELISPOT assays for both melanoma patients and healthy donors. In 1-week cocultures with DCs pulsed with 10 mug/ml peptide, MelanA/MART-1-specific T cells did not readily proliferate or differentiate into lytic effecters, in contrast to strong influenza-specific lytic responses. Therefore, despite distinct memory responses to influenza antigens, melanoma patients and healthy controls have a paucity of MA-reactive memory T cells, failing to rapidly generate IFN-gamma -secreting lytic effecters in shortterm assays, even when stimulated by DCs. |
| Keywords: | peptide; dendritic cells; in-vitro; lymphocytes; virus; vaccines; cd8(+); generation; elispot assay; high-frequencies; activation threshold |
| Journal Title: | Clinical Cancer Research |
| Volume: | 6 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2000-12-01 |
| Start Page: | 4831 |
| End Page: | 4838 |
| Language: | English |
| ACCESSION: | WOS:000166160200036 |
| PROVIDER: | wos |
| PUBMED: | 11156242 |
| Notes: | Article -- Source: Wos |
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