Exclusion of influences of ARMS2 polymorphisms on the central visual field in retinitis pigmentosa.

PURPOSE: To investigate the effects of polymorphisms of the age-related maculopathy susceptibility 2 (ARMS2) gene on the central visual field defects in retinitis pigmentosa (RP). SUBJECTS AND METHODS: The visual field was evaluated using the 10-2 Swedish Interactive Threshold Algorithm Fast Program and mean deviation (MD) slope, and regression coefficients of average sensitivity of the central 4 points (Cent4) were compared between each genetic subgroup. RESULTS: The MD slope (right/left) was as follows: GG, -1.37 ± 2.18/ -0.89 ± 1.15; GT, -0.56 ± 1.40/-0.77 ± 1.04; TT, -0.75 ± 0.64/ -0.38 ± 0.92 dB/year. The Cent4 was as follows: GG, -1.34 ± 2.37/-1.60 ± 3.21; GT, -1.15 ± 2.08/1.07 ± 1.80; TT, -1.20 ± 0.91/-0.65 ± 1.37 dB/year. No significant differences in the degree of progression were observed when comparing groups. CONCLUSIONS: These data suggest that polymorphisms of the ARMS2 do not modify the progression of the central field of vision in RP patients.

T-cell receptor Vbeta gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma.

We recently described that the SART-1(690-698) peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1(259) (+) tumor cells from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) cancer patients. In our study, in 5 of 14 HLA-A24(+) patients with oral squamous cell carcinomas (SCCs), CTLs could be induced with the SART-1(690-698) peptide from the PBMCs. In 2 of the patients from whom the highest CTL activities were induced, the T-cell receptor (TCR) Vbeta repertoire expressed by the SART-1(690-698)-specific CTLs was found to be restricted and multiple Vbeta families were predominantly expressed in each patient. Although the predominant Vbeta families were different between the 2 patients, Vbeta7 was highly and commonly predominant. The same predominant Vbeta families were also detected in the tumor-infiltrating lymphocytes (TILs) from each patient, and each Vbeta family contained one or more unique T-cell clonotypes. The unique T-cell clonotypes were found to be common between the TILs and SART-1(690-698)-specific CTLs from each patient, and especially 2 T-cell clonotypes with Vbeta7 were identical even in the 2 patients. One of the 2 T-cell clonotypes with Vbeta7 was detected in the TILs from 11 of 14 HLA-A24(+) patients and another was found in those from 8 of HLA-A24(+) patients, while none of 10 HLA-A24(-) patients demonstrated both T-cell clonotypes. These results strongly suggest that the T-cell clonotypes with Vbeta7 are major TCR Vbeta genes expressed by SART-1(690-698)-specific CTLs. Furthermore, autologous tumor cells from one of the HLA-A24(+) patients stimulated the PBMCs and regional lymph node cells (LNCs) to expand the same T-cell clonotypes as those in the SART-1(690-698)-specific CTLs. These results strongly suggest that the SART-1(690-698)-specific CTLs clearly accumulate in vivo, especially in the TILs, as a consequence of in situ antigenic stimulation by autologous tumor cells. The identification of the unique TCR Vbeta genes used by SART-1(259)-specific CTLs should help to improve the diagnosis of the specific immune response in patients with SART-1(259) (+) cancers, especially during anticancer immunotherapy.