Accumulation of Common T Cell Clonotypes in the Salivary Glands of Patients with Human T Lymphotropic Virus Type I-Associated and Idiopathic Sjögren’s Syndrome

Abstract

To clarify the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated Sjögren’s syndrome (SS), the TCR Vβ gene usage by the infiltrating lymphocytes in the target organ was examined. The Vβ families predominantly used in the labial salivary gland (LSG) from the HTLV-I-seropositive (HTLV-I+) SS patients were more restricted than those from the HTLV-I-seronegative (idiopathic) SS patients, and were commonly Vβ5.2, Vβ6, and Vβ7. The single-strand conformation polymorphism analysis revealed that T cell clonotypes with Vβ5.2, Vβ6, and Vβ7 accumulate in the LSG from the HTLV-I+ and idiopathic SS patients. Among junctional sequences of the most dominant Vβ7 transcripts, the conserved amino acid motif (QDXG: X is any amino acid) was found in six of the five HTLV-I+ SS patients and was also detected in two of the five idiopathic SS patients. Using the probes specific to the motif, the Vβ7 transcripts with the motif were detected in the LSG from all of the seven HTLV-I+ and five of the six idiopathic SS patients, but not from eight healthy subjects. The Vβ7 transcripts with this motif were also detected in the HTLV-I-infected T cell lines obtained from the LSG of an HTLV-I+ SS patient. The accumulation of HTLV-I-infected T cells expressing TCR with the conserved motif was thus indicated. These T cells were commonly present in patients with idiopathic SS and are strongly suggested to most likely be involved in the pathogenesis of both HTLV-I-associated and idiopathic SS. 1 This work was supported in part by grants from the Ministry of Education, Science, and Culture of Japan. Abbreviations used in this paper: HTLV-I, human T lymphotropic virus type-I; SS, Sjögren’s syndrome; LSG, labial salivary gland; PG, parotid gland; SSCP, single-strand conformation polymorphism; HAM/TSP, HTLV-I-associated myelopathy/tropical spastic paraparesis; HAAP, HTLV-I-associated arthropathy; CDR3, complementarity-determining region 3.

Tropical Spastic Paraparesis/Human T Leukemia Virus Type 1--Associated Myelopathy in HIV Type 1--Coinfected Patients

“…There appears to be some geographic variability in terms of other clinical signs, which may include visual disturbances, cranial nerve deficits, peripheral neuropathy, depressed ankle jerks, and cognitive dysfunction [26]. Virally mediated autoimmune injury involving other systems may be frequently observed in conjunction with TSP/HAM, including polymyositis, Sjögren syndrome, arthropathy, uveitis, interstitial pneumonitis, and thyroiditis [27][28][29][30][31][32]. Adult T cell leukemia caused by HTLV-1 has been infrequently diagnosed concomitantly with TSP/HAM [33,34].…”

Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease

“…Quantitative cDNA amplification was performed according to the recommendations of the manufacturer and as previously described (32)(33)(34). The cDNAs for the cytokines, chemokines, and chemokine receptors were analyzed by real-time PCR using LightCycler FastStart DNA Master SYBR Green 1 (Roche Diagnostics) in a LightCycler real-time PCR instrument (version 3.5; Roche Diagnostics).…”

“…All of the patients with Mikulicz disease and patients with SS RNA extraction and complementary DNA (cDNA) synthesis. Total RNA was prepared from the LSG specimens by the acid guanidinium-phenol-chloroform method as previously described (32)(33)(34). Three micrograms of the total RNA preparation was then used for the synthesis of cDNA.…”

Possible involvement of cytokines, chemokines and chemokine receptors in the initiation and progression of chronic GVHD

“…[11][12][13][14][15] The cDNA of cytokines, chemokines and chemokine receptors was analyzed by real-time PCR using LightCycler Fast Start DNA Master SYBR Green 1 (Roche Diagnostics, Mannheim, Germany) on a LightCycler real-time PCR instrument (version 3.5; Roche Diagnostics). The cytokines examined were IFN-g and IL-2, IL-4, IL-5 and IL-10.…”

“…The total RNA was prepared from the BM and LSG specimens and PBMC by the acidified guanidinium-phenol-chloroform method as previously described. [11][12][13][14][15] Three micrograms of the total RNA preparation was then used for the synthesis of cDNA. Briefly, RNA was incubated for 1 h at 42 1C with 20 U of RNasin ribonuclease inhibitor (Promega, Madison, WI, USA), 0.5 mg of oligo-(dT) 1218 (Pharmacia, Uppsala, Sweden), 0.5 mM of each dNTP (Pharmacia), 10 mM of DTT and 100 U of RNase H reverse transcriptase (Life Technologies, Gaithersburg, MD, USA).…”