Journal of Applied Genetics 42(4), 2001, pp. 531-540
Limited pattern of TCR delta chain gene rearrangement on the RNA level in multiple sclerosis
Jerzy NOWAK, Danuta JANUSZKIEWICZ, Monika PERNAK, Hanna HERTMANOWSKA, Karina NOWICKA-KUJAWSKA, Jolanta REMBOWSKA, Krzysztof LEWANDOWSKI, Tomasz NOWAK, Mieczyslaw WENDER
Abstract: Susceptibility to multiple sclerosis (MS) is most likely affected by a number of genes, including HLA and T-cell receptor (TCR) genes. T cells expressing g/d receptors seem to contribute to autoagression in MS, as evidenced by their localization in the MS plaques in the brain. The aim of this study was to analyse the TCRd chain gene rearrangement at the RNA (cDNA) level and compare to the DNA pattern rearrangement. TCRd gene rearrangement was analysed in MS patients and healthy individuals with the use of primers specific for Vd1-6 and Jd1 genes (at the DNA level) and specific for Vd1-6 and Cd1 genes (at the cDNA level). The size of PCR products was analysed on agarose gel and by ALF-Express (Pharmacia). Additionally, the lymphocyte surface immunophenotype was studied with specific monoclonal antibodies. At the DNA level a restricted pattern of Vd3-Jd1 and Vd5-Jd1 was found only in MS patients. Contrary to DNA, mono-, oligoclonal RNA (cDNA) rearrangements were limited to Vd1-Cd1, Vd2-Cd1 and Vd3-Cd1 only in MS patients as well. Surface immunophenotype analysis revealed in MS a much higher frequency of activated g/d T lymphocytes, i.e. expressing HLA-DR and CD25. An elevated level of CD56 positive cells in MS was recorded. Mono-oligoclonal pattern of TCRd gene rearrangement at the RNA level, along with increase in activated g/d T cells, strongly argue for a significant role of g/d T lymphocytes in the pathogenesis of MS.
Key words: multiple sclerosis, T cell receptor rearrangement, TCRd.
Correspondence: J. NOWAK, Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszynska 32, 60-479 Poznan, Poland; e-mail: firstname.lastname@example.org