TABLE 5.
Detection of HPV16 E7-reactive CD8+ T cells in healthy individuals and patients with carcinoma in situa
| Group and donor no. | CD3+ CD8+ (%) | HPV (%) | CMV (%) |
|---|---|---|---|
| Healthy individuals | |||
| 1 | 18 | 0 | 0.03 |
| 2 | 24 | 0 | 0 |
| 3 | 16 | 0 | 0.1 |
| 4 | 15 | 0 | 0.12 |
| 5 | 14.6 | 0.02 | NDb |
| 6 | 8.37 | 0.41 | ND |
| 7 | 19.1 | 0.11 | ND |
| 8 | 11.5 | 0.13 | ND |
| 9 | 18.2 | 0.18 | ND |
| 10 | 38 | 0.1 | 0 |
| Patients with carcinoma | |||
| 1 | 21.8 | 0.06 | 0.10 |
| 2 | 15.4 | 0.03 | 0.03 |
| 3 | 21.2 | 0.03 | 0.01 |
| 4 | 8.89 | 0.04 | 0.03 |
| 5 | 15.9 | 0.01 | 0.00 |
| 6 | 27.4 | 0.04 | 0.00 |
| 7 | 11.9 | 0.08 | 0.32 |
| 8 | 9.73 | 0.02 | 0.02 |
| 9 | 16.1 | 0.06 | 0.00 |
| 10 | 20.3 | 0.6 | 0.8 |
PBL, TIL, or T cells from tumor-draining lymph nodes were isolated, gated on CD3+ CD8+ T cells as indicated, and tested for the frequency of HPV16-E711-19 or CMVpp65 binding T cells using HLA-A2 tetramer complexes. Note the high frequency of HPV16 E7 staining T cells in healthy individuals and the low numbers of HPV-reactive T-cells in the CD8+ T-cell population in patients with preinvasive cervical cancer or in PBL from patients with invasive cervical cancer (see Table 6). Data for tetramer-reactive T cells showing ≥ 0.1 frequency in CD3+ CD8+ are shown in bold face type. In contrast to HPV-specific T cells, 7 of 18 patients with cervical cancer showed CD8+ T cells (≥ 0.1%) binding to the CMVpp65 T-cell epitope. Low numbers of HPV-reactive T cells could be detected in TIL or in tumor draining lymph nodes (see Table 6). All individuals are HLA-A2+, and HPV16 DNA was present in the tumor lesions of all patients with CIN, as detected by PCR analysis. PBL from healthy individuals (donors 5 to 7), patients with CIN (donors 4 and 7), or patients with cervical cancer (donors 6, 8, 13, and 16 in Table 6) were restimulated in vitro either with the HPV16 E7 wild-type epitope YMLDLQPET or with the coronavirus-derived peptide TMLDIQPED using HLA-A2-matched dendritic cells as antigen-presenting cells in order to test if the number of HPV tetramer-reactive T cells could be increased. No significant increase of tetramer-binding T cells could be observed in any of the in vitro culture assays (data not shown).
ND, not determined.