Polyclonal integration of HTLV‐I proviral DNA in lymphocytes from HTLV‐I seropositive individuals: an intermediate state between the healthy carrier state and smouldering ATL

Abstract

We have studied 15 individuals (aged 14-74 years) with antibodies to HTLV-I in their serum and random integration of HTLV-I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non-specific complaints which did not correspond to those of adult T-cell leukemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV-I infection; 25% of their family members were also seropositive for HTLV-I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal. These individuals with polyclonal integration of HTLV-I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV-I carriers (with antibodies but no detectable HTLV-I proviral DNA). Patients with this intermediate state of HTLV-I infection may be at risk to progress to ATL. The natural history of HTLV-I infection in humans leading to the development of ATL is reviewed in the light of these new findings.

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

“…Interestingly, a monoclonal integration of the HTLV provirus in peripheral blood mononuclear cells (PBMCs), as evidenced by Southern blotting, has been reported in about 40% of HTLV-1 carriers with strongyloidiasis . By contrast, Southern-blotting, which has a sensitivity of about 1/20, failed to detect any signal in HTLV-1 infected individuals without strongyloidiasis (Chen et al, 1995;Nakada et al, 1987;Yamaguchi et al, 1988). In addition, Ss has been found to signi®cantly shorten the incubation period of ATLL, which occurs 30 years earlier in HTLV-1 individuals with strongyloidiasis than in other HTLV-1 asymptomatic carriers (Cleghorn et al, 1995;Plumelle et al, 1997;Pombo de Oliveira et al, 1995;Yamaguchi et al, 1987).…”

HTLV‐1 provirus load in peripheral blood lymphocytes of HTLV‐1 carriers is diminished by green tea drinking

“…Individuals with a higher provirus load, who are at risk for ATL, may derive particular benefit from green tea drinking because they have increased number of abnormal lymphocytes that are prone to apoptosis. 22,29,33) "Nanchariki" is made of whole extract of green tea, which contains caffeine and polyphenol compounds. Decaffeinated capsules of green tea extract powder may minimize in the effects on the stomach and bowel movements encountered in the drop-out cases in this study.…”

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

“…Chronic, usually asymptomatic, gastrointestinal infections are found in most otherwise healthy individuals, however, in immunocompromised hosts or patients on immunosuppressive therapy, extreme multiplication of the parasite occurs with dissemination of larvae in the body (Neva, 1986;Grove, 1996). Strongyloidiasis is relatively common in tropical and subtropical areas such as the West Indies and in Okinawa, Japan, where HTLV-1 is also endemic (Patey et al, 1992;Satoh et al, 1991), and it is frequently associated with lymphoid malignancies, including ATL (Yamaguchi et al, 1988;Patey et al, 1992).…”

“…The increased number of HTLV-1-infected cells in the peripheral blood was shown to be the result of polyclonal expansion of infected cells (Greenberg et al, 1989;Gessain et al, 1990;Ono et al, 1995). In the context of ATL, a condition associated with an increased provirus load was clinically considered to be an intermediate state and is often complicated by opportunistic infection, such as strongyloidiasis or mycosis (Yamaguchi et al, 1988). The intermediate state was also considered to be a preleukemic state because ATL developed among carriers in an intermediate state during follow-up (Patey et al, 1992).…”