Publication Date:
2008-11-16
Description:
Human T-cell leukemia virus-1 (HTLV-1) is the first human retrovirus that has infected approximately 10–20 million people worldwide and causes adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) after long-term chronic infection. The immune response to HTLV-1 is typically enhanced in HAM/TSP, while impaired cell-mediated immunity has been identified as a causative basis of immunodeficiency in ATLL. The negative immuno-regulatory program death-1 (PD-1) signaling is involved in auto-immunity, allergy, sites of immune privilege, and antitumor immunity. We have previously reported decreased frequency and function of HTLV-1 Tax-specific CD8+ T-cell in ATLL patients due to insufficient cytolytic effector molecules, as well as upregulated PD-1 expression on HTLV-1-specific CTLs from asymptomatic carriers (ACs) and ATLL patients. That PD-1 expression was significantly higher on HTLV-1 specific CD8+ T-cells, as well as CMV− and EBV-specific CTLs in ATLL patients compared to ACs, suggested that PD-1 signaling plays a role in fostering persistent HTLV-1 infections, facilitating immune evasion by ATLL cells, which may further ATLL development (ASH annual meeting 2006, 2007). However, there is no report on the repertoir and PD-1 expression of HTLV-1-specific CTL in carriers with hyper immune states such as collagen disease or HAM/TSP. Therefore, to characterize HTLV-1-specific CTL in asymptomatic HTLV-1 carriers (ACs), carriers with collagen disease (CCs) and HAM/TSP patients, we examined the frequency, diversity and PD-1 expression of HTLV-1-specific CTL in 23 ACs, 33 carrier with collagen vascular disease, 40 HAM/TSP patients and 18 healthy donors (HDs) using 16 distinct HTLV-1 Tax/Env HLA-A*0201 and HLA-A*2402 tetramers. The difference in frequency of HTLV-1 Tax-specific CTL positivity was not statistically significant between CCs, HAM/TSP or ACs. In contrast, HTLV-1 Env-specific CTL were significantly more frequent in autoimmune disorders and HAM/TSP than those in ACs (Table 1). On the other hand, percentages of CD8+ lymphocytes from these carriers expressing PD-1 were significantly higher than that from HDs. Futhermore, the rates of PD-1 expression on CMV- or EBV-specific CTL in CCs, HAM/TSP and ACs were similar although PD-1 expression was significantly down-regulated on HTLV-1-specific CTL in CCs and HAM/TSP compaired to ACs (Figure1, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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