Study of Immunomechanisms in HTLV-I-Associated Myelopathy(HAM)

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Purpose :To clarify the pathogenesis of HTLV-I-associated myelopathy (HAM), we studied several immunological abnormalities which were frequently observed in the patients and were thought to be changes characteristic of this disease. In this study, we mainly studied (1) an alteration of subsets of the peripheral blood mononuclear cells (PBMNC), (2) a great increase in spontaneous proliferation of the peripheral blood lymphocytes (PBL), and (3) cellular immune surveillance against increased HTLV-I infected cells in the peripheral circulation of the patients.Results :(1) Subsets of PBMNC ; We found a significant increase in activated T-lymphocytes (CD25+CD3+ cells, CD4+DR+ cells and CD8+DR+ cells) and helper inducer T-lymphocytes (CD4+CD29+ cells) in the peripheral blood of HAM patients. This increase in activated T-lymphocytes and helper T-lymphocytes became more prominant when PBMNC were cultured in a short term. There were decreases in several subsets of NK cells, such as CD16+ cells, … More CD56+ cells and CD16+CD3+ cells.(2) Study of an increased spontaneous PBL proliferation ; We observed a great increase in spontaneous PBL proliferation (SPP) in a short-term culture of PBMNC from HAM patients, without any mitogens or antigens. In the suppression study of the SPP, either the sera from patients or monoclonal antibodies (mAb) to HTLV-I did not suppress the increased SPP. In contrast, mAb to IL-2R (CD25) and cyclosporin A (an inhibitor of IL-2 production) showed strong suppression effects on SPP.(3) Cellular immune surveillance against HTLV-I infected cells ; We observed that HTLV-I proviral DNA was significantly increased in PBMNC from HAM patients compared with those from HTLV-I carriers. To evaluate an ability of the cellular immune surveillance against HTLV-I infected cells, we studied NK activity and CTL and ADCC activities against HTLV-I infected cells. Although CTL activity was significantly higher in HAM patients than in carriers, NK and ADCC activities were significantly decreased in the patients.Conclusions :In the peripheral circulation of HAM patients, HTLV-I infected cells were increased and T-lymphocytes were found in highly activated state. A great increase in SPP is a characteristic change observed in HAM, and the SPP may induce several autoreactive T-cell clones reactive to CNS tissue. Less