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J Immunol ; 162(3): 1765-71, Feb. 1, 1998.
Artigo em Inglês | MedCarib | ID: med-1370


Human T cell lymphotropic virus-I (HTLV-I) -associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetrameters loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR beta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.(Au)

Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T CD8-Positivos/imunologia , Produtos do Gene tax/química , Produtos do Gene tax/imunologia , Antígeno HLA-A2/química , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Paraparesia Espástica Tropical/imunologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Antígenos CD28/metabolismo , Antígeno B7-1/metabolismo , Ativação Linfocitária , Paraparesia Espástica Tropical/genética , Fenótipo , Conformação Proteica , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Quimiocinas/metabolismo , Receptores de Interleucina-2/metabolismo , Solubilidade
Blood ; 86(11): 4063-75, Dec.1 1995.
Artigo em Inglês | MedCarib | ID: med-1757


Adult T-cell leukemia (ATL) is a malignancy of mature lumphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months: no chemotherapy regimen appears successful inducing long-term disease-free survival. The scientific basis of the present study is the ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this differnce, we administered anti-Tac armed with Yttrium-90 (Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5-to 15-mCi doses used, 9 of 16 evaluable patients responded to Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.(AU)

Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Humanos , Masculino , Vírus Linfotrópico T Tipo 1 Humano/efeitos da radiação , Receptores de Interleucina-2/uso terapêutico , Radioimunoterapia , Radioisótopos de Ítrio/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Estados Unidos , Jamaica , Trinidad e Tobago , Guiana , Japão , Haiti , Granada , São Vicente e Granadinas , Estudos Transversais
Br J Haematol ; 89(3): 615, Mar. 1995.
Artigo em Inglês | MedCarib | ID: med-5892


We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older siblings had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents and the development of ATLL in second-generation Caribbean immigrants (AU)

Relatos de Casos , Humanos , Masculino , Feminino , Leucemia-Linfoma de Células T do Adulto/transmissão , Transmissão Vertical de Doença Infecciosa , Antígenos CD4/sangue , Afro-Americanos , Saúde da Família , Leucemia-Linfoma de Células T do Adulto/etnologia , Leucemia-Linfoma de Células T do Adulto/patologia , Linfonodos/patologia , Linhagem , Receptores de Interleucina-2/análise , Trinidad e Tobago/etnologia