The usage of T-cell-receptor (TCR) alpha beta variable (V) regions among tumor infiltrating lymphocytes (TILs) in primary human malignant melanomas was characterized using a method based on the polymerase chain reaction (PCR). A panel of 57 different variable-region primers specific for the TCR V alpha I-29 and V beta I-28 was designed, and a semi-quantitative PCR method applicable to formalin-fixed, paraffin-embedded tissues was developed. This semi-quantitative method was demonstrated to be reproducible and to be useful for the assessment of V alpha- and V beta-gene-family usage in formalin-fixed, paraffin-embedded tissue samples. A total of 9 different histopathologically characterized primary tumors were analyzed in this study. The TILs in these tumors were found to preferentially express certain TCR V alpha and V beta regions. The differential usage of certain V alpha regions was very pronounced as illustrated by V alpha 4, which was highly expressed in 3/8 tumors, and V alpha 22, which was highly expressed in 4/8 tumors. For comparison, specific highly expressed V alpha regions in control samples of peripheral-blood lymphocytes rarely exceeded 10%. The most highly expressed V beta region was V beta 8, which was highly expressed in 2/8 tumors. For the highly expressed V alpha 4 and V alpha 22 and V beta 8 regions, the high levels may be explained by the in situ clonal or oligoclonal expansion of TIL. In one specific case, the high expression of V beta 8 was due to expansion of a single clone of TILs, as evidenced by a fully readable sequence of the CDR3 (V-D-J) region, determined by direct sequencing of the PCR product corresponding to V beta 8. In contrast, sequence analysis of V alpha 22, which was expressed in the same tumor sample at similar levels, demonstrated the simultaneous presence of 3 different CDR3 (V-J) sequences derived from V alpha 22 transcripts of exactly the same length. The observed preferential use of TCR V alpha and V beta regions suggests the in situ clonal expansion of specific populations of T-cells, possibly reactive with melanoma-associated peptides presented by HLA molecules. The preferential use of TCR V alpha and V beta regions may imply the involvement of a limited number of shared melanoma-associated peptides.
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http://dx.doi.org/10.1002/ijc.2910560115 | DOI Listing |
Front Physiol
January 2025
Plant Protection Institute, Hebei Academy of Agriculture and Forestry Sciences, Key Laboratory of Integrated Pest Management on Crops in Northern Region of North China, Ministry of Agriculture and Rural Affairs, IPM Innovation Center of Hebei Province, International Science and Technology Joint Research Center on IPM of Hebei Province, Baoding, China.
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Int J Nanomedicine
January 2025
College of Chemical and Material Engineering, Quzhou University, Quzhou, Zhejiang Province, 324000, People's Republic of China.
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March 2025
Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Objective: Osteoarthritis, a degenerative joint disease, requires innovative therapies due to the limited ability of cartilage to regenerate. Since mesenchymal stem cells (MSCs) provide a cell source for chondrogenic cells, we hypothesize that chemicals capable of enhancing the chondrogenic potential of MSCs with transforming growth factor-beta (TGFβ) in vitro may similarly promote chondrogenesis in articular cartilage in vivo.
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Front Pharmacol
January 2025
Key Research Laboratory for Prevention and Treatment of Cerebrospinal diseases, Shaanxi Provincial Administration of Traditional Chinese Medicine, Xianyang, China.
Purpose: Xixin Decoction (XXD) is a classical formula that has been used to effectively treat dementia for over 300 years. Modern clinical studies have demonstrated its significant therapeutic effects in treating Alzheimer's disease (AD) without notable adverse reactions. Nevertheless, the specific mechanisms underlying its efficacy remain to be elucidated.
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January 2025
Lisa-Kolk-Stiftung, Berg. Neukirchen, North Rhine Westphalia, 51381, Germany.
Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection.
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