Construction of CAR-T cells targeting CS1 and analysis of their antitumor activity in vitro / 生物工程学报

We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.

Serial evaluation of percentage of activated T-lymphocytes in peripheral blood of human immunodeficiency virus infected individuals as a prognostic marker

Immune activation often associated with human immunodeficiency virus [HIV] infection is characterized by increasing number of peripheral blood T-lymphocytes expressing HLA-DR molecule. This study was performed to investigate the changes in the percentage of activated lymphocytes in the peripheral blood of HIV infected patients on antiretroviral therapy. Routine flow cytometry data for peripheral blood lymphocyte subsets were analyzed in 11 HIV infected hemophilia patients [mean age 27 +/- 7] at approximately 6 monthly intervals from 1996 to 2002 in the Division of Immunology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia. The number of data sets for each individual was variable, ranging between 5-13. Percentages of each lymphocyte subset were extracted and correlations were sort by using linear regression analysis. Proportion of activated T-lymphocytes in the peripheral blood was initially high. Over a period of 2-5 years the percentage of T-lymphocytes, expressing HLA-DR molecule was found to have decreased significantly [P < / =0.0001] in all the patients most probably as a result of antiretroviral therapy. There was no statistically significant change in the proportion of any other lymphocyte subtype studied. The reduction in the percentage of HLA-DR+ T-lymphocyte population inversely correlated with CD4/CD8 ratios in 8 and for the CD4+ lymphocyte proportions with 5 out of 11 patients, whereas positive correlation for CD8+ lymphocyte proportions was noted in 4 patients. These findings confirm immune activation in HIV infection with the increasing percentage of HLA-DR+ T-lymphocytes in the peripheral blood. Declining activated T-lymphocyte proportion in the peripheral blood and its inverse correlation with CD4/CD8 ratio may be more sensitive in detection of changes in CD4+ and CD8+ lymphocyte populations in HIV infection serving as a prognostic marker

Estudo imunohistoquímico da gengivite-HIV / Immunohistochemical study of HIV-gingivitis

A infecçäo pelo vírus HIV induz profundas alteraçöes no sistema imune do hospedeiro, incluindo perda dos linfócitos T CD4+, supressäo das respostas a antígenos T-dependentes e ativaçäo anormal dos linfócitos B. Diversas entidades patológicas säo observadas durante o curso da infecçäo por este vírus, sendo que algumas destas, como a doença periodontal inflamatória (DPI), apresentam alto grau de morbidade. Alguns estudos clínicos e microbiológicos demonstram importantes diferenças entre a gengivite-HIV e a gengivite inespecífica (pacientes HIV-negativos), embora a nível histopatológico näo exista nenhum estudo comparativo entre elas. O objetivo deste trabalho foi avaliar quantitativamente o número de linfócitos T, linfócitos T "auxiliares", linfócitos B, macrófagos, células de Langerhans, neutrófilos, plasmócitos secretores de IgG, IgM, IgE e IgA na gengivite-HIV comparado com a gengivite inespecífica. Esta avaliaçäo foi baseada na identificaçäo imunohistoquímica pela Técnica da Streptavidina-Biotina dos seguintes antígenos: CD3 (linfócitos T), OPD4 (linfócitos T "auxiliares"), CD20 (linfócitos B), CD68 (macrófagos), S-100 (células de Langerhans), elastase (neutrófilos), IgG, IgM, IgE e IgA (plasmócitos secretores de IgG, IgM, IgE e IgA, respectivamente). Os resultados mostraram maior percentual de linfócitos T, linfócitos T "auxiliares" e macrófagos na gengivite inespecífica. O número de células intraepiteliais S-100 positivas ( células de Langerhans) por campo foi maior também na gengivite inespecífica comparado com a gengivite-HIV. A gengivite-HIV apresentou percentuais maiores de plasmócitos IgG positivos e neutrófilos em relaçäo à gengivite inespecífica. Estes resultados indicam que a severidade da DPI em pacientes HIV-positivos deve estar relacionada com a própria imunodepressäo celular presente na doença e enfatizam a importância dos linfócitos T na defesa do periodonto. Os dados encontrados sugerem também que a predominância de plasmócitos e neutrófilos no infiltrado inflamatório periodontal constitui um quadro mais compatível com lesäo destrutiva

The association of adenosine deaminase activity with T-lymphocytes and subsets in pulmonary tuberculosis and bronchogenic carcinoma.

Simultaneous determination of blood/lung ADA activity and T-lymphocyte subsets was conducted in 12 patients with active pulmonary tuberculosis, 12 patients with bronchogenic carcinoma and 11 healthy volunteers. Differences were significant only in the tuberculosis patients, namely, increased mean enzyme values in both the peripheral blood (36.68 +/- 10.90 U/L) and in the BALF (4.25 +/- 2.19 U/L), and correlation of ADA activity between the blood and the diseased lung only; the difference in elevated enzymatic activity between the tuberculosis group and the cancer group was of no statistical significance. We conclude that simultaneous ADA analysis of the blood and the BALF may be of diagnostic value in cases suspected of having tuberculosis as yet undiagnosed by other means. Based on the lowest value of enzymatic activity in the blood of patients with tuberculosis (28 U/L), the test has a sensitivity of 75 per cent and a specificity of 100 per cent; whereas the lowest value in the BALF of tuberculosis patients (2.9 U/L), the test has a sensitivity of 77 per cent and a specificity of 82 per cent. Findings that there was a blood-lung correlation of elevated ADA activity and a correlation of enzymatic elevation with increased numbers of T-cells bearing IL-2 receptor in cases of pulmonary tuberculosis only provide evidence in support of T-lymphocytes actively participating in the ongoing immune process.