Clonotypic surface structure on human T lymphocytes: functional and biochemical analysis of the antigen receptor complex.

Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to identification of the human T cell antigen receptor as a surface complex comprised of a clonotypic 90KD Ti heterodimer and the monomorphic 20/25KD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and fully expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. The presence of unique peptides following proteolysis of different Ti molecules isolated by noncrossreactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and beta subunits. Moreover, N-terminal amino acid sequencing of the Ti beta subunit shows that it bears homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand (antigen/MHC), enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor crosslinking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors

Respiratory complications in Brazilian patients infected with human immunodeficiency virus Complicações respiratórias em pacientes brasileiros infectados pelo vírus da imunodeficiência humana

PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV) infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents. PATIENTS AND METHODS: Thirty-five HIV seroposiüve subjects with respiratory complaints were studied. All patients had a complete history, physical examination and blood counts. The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Patients with treatable complications received standard antimicrobial therapy. RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis. The sputum examination identified the pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy. The most frequently identified microorganism was P. carinii (55%), followed by M. tuberculosis (41%) and cytomegalovirus (8%). The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens. Twenty-three individuals with P. carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV. The histologic evaluation was crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease. However, most of the features observed in HIV infected patients had been previously described in infection of the normal host. Furthermore, the AIDS subjects showed a good therapeutic response to anti-tuberculous drugs.<br>OBJETIVO: Determinar a frequência e os meios pelos quais é possível identificar um agente patogênico respiratório em pacientes brasileiros infectados pelo vírus da imunodeficiência humana (HIV); quais são os microorganismos mais comuns; e qual é o impacto da terapêutica específica. PACIENTES E MÉTODOS: Trinta e cinco pacientes HIV positivos, com queixas respiratórias foram estudados. Todos os pacientes tiveram história, exame físico e testes hematólogicos. A avaliação da patologia respiratória incluiu radiografia pulmonar, exame do escarro para bactérias e fungos, broncoscopia com lavagem bronquiolo-alveolar e biopsia transbronquica. Pacientes com patologias tratáveis receberam a terapêutica indicada. RESULTADOS: Um ou mais organismos foram encontrados em 24 pacientes, e outros 3 pacientes mostraram pneumonite intersticial inespecífica. O exame de escarro identificou o agente patogênico pulmonar em 7 casos. O lavado bronquiolo-alveo-lar e o exame histopatológico definiram o diagnóstico em 14% e 83%, respectivamente, entre os 28 pacientes que foram submetidos à broncoscopia. O organismo mais comun foi P.carinii (55%), seguido por M.tuberculosis (41%), e citomegalovírus (8%). Os achados clínicos, laboratoriais e radioló-gicos não discriminaram os agentes patogênicos. Vinte e três pacientes com PCP ou tuberculose receberam terapêutica específica; entre os pacientes que puderam ser avaliados o tratamento foi bem sucedido em 79% dos episódios de PCP e 100% em TB. CONCLUSÕES: Determinamos que TB, PCP e CMV são as causas mais frequentes de infecções respiratórias em pacientes brasileiros infectados pelo HIV. O exame histológico foi essencial para firmar o diagnóstico etiológico. A TB em pacientes aidéticos assumiu formas semelhantes à TB primária em pacientes imunocompetentes e apresentou boa resposta terapêutica