Interferon beta transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens
被引:27
作者:
Vieillard, V
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机构:UNIV PARIS 11,INST CURIE,CNRS,UNITE MISTE RECH 177,F-91405 ORSAY,FRANCE
Vieillard, V
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机构:
Cremer, I
Lauret, E
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机构:UNIV PARIS 11,INST CURIE,CNRS,UNITE MISTE RECH 177,F-91405 ORSAY,FRANCE
Lauret, E
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机构:
Rozenbaum, W
Debre, P
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机构:UNIV PARIS 11,INST CURIE,CNRS,UNITE MISTE RECH 177,F-91405 ORSAY,FRANCE
Debre, P
Autran, B
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Autran, B
DeMaeyer, E
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机构:UNIV PARIS 11,INST CURIE,CNRS,UNITE MISTE RECH 177,F-91405 ORSAY,FRANCE
DeMaeyer, E
机构:
[1] UNIV PARIS 11,INST CURIE,CNRS,UNITE MISTE RECH 177,F-91405 ORSAY,FRANCE
[2] HOP ROTHSCHILD,F-75012 PARIS,FRANCE
[3] HOP LA PITIE SALPETRIERE,CNRS,UNITE RECH ASSOCIEE 625,F-75011 PARIS,FRANCE
gene therapy;
retroviral vector;
human CD4(+) cells;
immunology;
D O I:
10.1073/pnas.94.21.11595
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) beta. Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-H(b)HuIFN beta retroviral vector. The constitutive low production of IFN-beta in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4(+) cells, and this protective effect was observed only in the PBL derived from donors having a CD4(+) cell count above 200 per mm(3). In IFN-beta-transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-gamma and interleukin (IL)-12 was enhanced, In IFN-beta-transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor alpha was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL, The proliferative response to recall antigens was partially restored in IFN-beta-transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-beta transduction of PBL from HIV-infected donors improves several parameters of immune function.