Resistance of CIN-positive T lymphocytes to etoposide-induced apoptosis mediated by upregulation of Bcl-xL expression in patients with HTLV-I-associated myelopathy

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) is c haracterized by chronic inflammation of the spinal cord. The exact mechanis ms that enhance the development of chronic myelopathy remain to be determin ed. One such mechanism could be an altered response of peripheral blood CD4 (+) T lymphocytes to apoptotic stimuli. We examined the sensitivity of thes e cells to apoptosis in HAM patients and control. Apoptosis was induced by etoposide, which induces mitochondria-dependent apoptosis through the relea se of cytochrome c from the mitochondria. The percentage of apoptotic cells that expressed hypodiploid DNA among etoposide-treated CD4(+) T lymphocyte s was significantly lower in HAM patients than in the control. Western blot analysis of cell lysates derived from CD4(+) T lymphocytes demonstrated th at the expression level of Bcl-xL protein was significantly higher in HAM p atients than in the control. Our results indicate that peripheral blood CD4 + T lymphocytes of HAM patients are resistant to apoptosis triggered throug h mitochondrial death pathway through upregulation of expression of anti-ap optotic protein, Bcl-xL. This phenomenon might contribute to the prolongati on and perpetuation of the chronic inflammatory process in the spinal cord of HAM patients. (C) 2001 Elsevier Science B.V. All rights reserved.