An anti-CD45RO immunotoxin eliminates T cells latently infected with HIV-1 in vitro

被引:27
作者
McCoig, C
Van Dyke, G
Chou, CS
Picker, LJ
Ramilo, O
Vitetta, ES
机构
[1] Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Grad Program Immunol, Dallas, TX 75235 USA
[3] Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75235 USA
[4] Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA
[5] Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75235 USA
关键词
D O I
10.1073/pnas.96.20.11482
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
Despite the success of highly active antiretroviral therapy (HAART) in lowering circulating HIV-1 to undetectable levels in most infected individuals, several studies have documented the presence of a small reservoir of latently infected cells in HAART patients, the majority of which are CD45RO(+) memory T cells. We previously have demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25(+) cells with an immunotoxin (IT), The present study was designed to determine whether these latent cells could be eliminated by an anti-CD45RO IT. Our results indicate that the anti-CD45RO IT eliminates >99%, of either M-tropic or T-tropic virus produced by the latently infected cells after mitogen stimulation. This IT also appears to be as effective as the anti-CD25 IT in eliminating the activated, HIV-1-producing cells, In contrast, the anti-CD45RO IT does not kill CD45RA(+) naive cells. Further studies using cells from HIV-1-infected individuals on HAART will be necessary to determine the potential clinical utility of this IT.
引用
收藏
页码:11482 / 11485
页数:4
相关论文
共 34 条
[11]  
Collins RH, 1997, EXP HEMATOL, V25, P147
[12]   Changes in thymic function with age and during the treatment of HIV infection [J].
Douek, DC ;
McFarland, RD ;
Keiser, PH ;
Gage, EA ;
Massey, JM ;
Haynes, BF ;
Polis, MA ;
Haase, AT ;
Feinberg, MB ;
Sullivan, JL ;
Jamieson, BD ;
Zack, JA ;
Picker, LJ ;
Koup, RA .
NATURE, 1998, 396 (6712) :690-695
[13]   IMMUNOTOXINS CONSTRUCTED WITH ANTI-CD25 MONOCLONAL-ANTIBODIES AND DEGLYCOSYLATED RICIN A-CHAIN HAVE POTENT ANTITUMOR EFFECTS AGAINST HUMAN HODGKIN CELLS-INVITRO AND SOLID HODGKIN TUMORS IN MICE [J].
ENGERT, A ;
MARTIN, G ;
AMLOT, P ;
WIJDENES, J ;
DIEHL, V ;
THORPE, P .
INTERNATIONAL JOURNAL OF CANCER, 1991, 49 (03) :450-456
[14]   Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy [J].
Finzi, D ;
Blankson, J ;
Siliciano, JD ;
Margolick, JB ;
Chadwick, K ;
Pierson, T ;
Smith, K ;
Lisziewicz, J ;
Lori, F ;
Flexner, C ;
Quinn, TC ;
Chaisson, RE ;
Rosenberg, E ;
Walker, B ;
Gange, S ;
Gallant, J ;
Siliciano, RF .
NATURE MEDICINE, 1999, 5 (05) :512-517
[15]   Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy [J].
Finzi, D ;
Hermankova, M ;
Pierson, T ;
Carruth, LM ;
Buck, C ;
Chaisson, RE ;
Quinn, TC ;
Chadwick, K ;
Margolick, J ;
Brookmeyer, R ;
Gallant, J ;
Markowitz, M ;
Ho, DD ;
Richman, DD ;
Siliciano, RF .
SCIENCE, 1997, 278 (5341) :1295-1300
[16]   HIV-protease inhibitors [J].
Flexner, C .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (18) :1281-1292
[17]   Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy [J].
Furtado, MR ;
Callaway, DS ;
Phair, JP ;
Kunstman, KJ ;
Stanton, JL ;
Macken, CA ;
Perelson, AS ;
Wolinsky, SM .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (21) :1614-1622
[18]   Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy [J].
Gulick, RM ;
Mellors, JW ;
Havlir, D ;
Eron, JJ ;
Gonzalez, C ;
McMahon, D ;
Richman, DD ;
Valentine, FT ;
Jonas, L ;
Meibohm, A ;
Emini, EA ;
Chodakewitz, JA .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (11) :734-739
[19]   A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less [J].
Hammer, SM ;
Squires, KE ;
Hughes, MD ;
Grimes, JM ;
Demeter, LM ;
Currier, JS ;
Eron, JJ ;
Feinberg, JE ;
Balfour, HH ;
Dayton, LR ;
Chodakewitz, JA ;
Fischl, MA .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (11) :725-733
[20]   Rate of HIV-1 RNA rebound upon stopping antiretroviral therapy [J].
Harrigan, PR ;
Whaley, M ;
Montaner, JSG .
AIDS, 1999, 13 (08) :F59-F62