A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging

OBJECTIVE: Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. MATERIALS AND METHODS: This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. RESULTS: A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). CONCLUSION: The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.

Subdominant H60 antigen-specific CD8 T-cell response precedes dominant H4 antigen-specific response during the initial phase of allogenic skin graft rejection

In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.

Characterization of CTL Clones Specific for Single Antigen, H60 Minor Histocompatibility Antigen

BACKGROUND: Disparities of Minor H antigens can induce graft rejection after MHC-matched transplantation. H60 has been characterized as a dominant antigen expressed on hematopoietic cells and considered to be an ideal model antigen for study on graft-versus-leukemia effect. METHODS: Splenocytes from C57BL/6 mice immunized with H60 congenic splenocytes were used for establishment of H60-specific CTL clones. Then the clones were characterized for proliferation capacity and cytotoxicity after stimulation with H60. Clone #14, #15, and #23 were tested for the TCR binding avidity to H60-peptide/H-2Kb and analyzed for TCR sequences. RESULTS: H60-specific CTL clones showed different levels of proliferation capacity and cytotoxic activity to H60-stimulation. Clones #14, #15, and #23 showed high proliferation activity, high cytotoxicity, and low activities on both aspects, respectively, and have TCRs with different binding avidities to H60-peptide/H-2Kb with t 1/2 values of 4.87, 6.92, and 13.03 minutes, respectively. The TCR usages were Valpha12D-3-01+Jalpha11-01 and Vbeta12-1-01+Dbeta1-01+J2-7-01 for clone #14, Valpha13D-1-02+Jalpha34-02 and Vbeta13-1-02+Dbeta2-01+Jbeta2-7-01 for clone #15, and Valpha16D+Jalpha45-01 and Vbeta12-1-01+Dbeta1-01+Jbeta2-5-01 for clone #23. CONCLUSION: The results will be useful for modeling GVL and generation TCR transgenic mouse.