The potential roles of 4-1BB costimulation in HIV type 1 infection.
The potential role of 4-1BB in human immunodeficiency virus (HIV-1)-infected T cells was investigated with HIV-1-infected subjects. 4-1BB expression was readily inducible on PHA stimulation of T cells from HIV-1-infected individuals. The level of 4-1BB expression and the percentage of 4-1BB-expressing T cells were higher in HIV-1+ individuals than in the HIV-1- controls (p < 0.01). The difference in 4-1BB expression was more significant in CD8+ T cells and the high level of 4-1BB expression was correlated with low CD4+ T cell counts (r = -0.63, p < 0.05). 4-1BB signal cooperated with CD28 for proper HIV-1+ CD4+ T cell proliferation. In addition, cross-linking 4-1BB with agonistic monoclonal antibody enhanced HIV-1 replication both in primary stimulation and secondary restimulation of CD4+ T cells from HIV-1+ individuals. To test whether 4-1BB cross-linking signals an activation of HIV-1, J8-1, a 4-1BB+ Jurkat subline, was transiently transfected with pHIV-1-LTR-CAT plasmid and stimulated through 4-1BB. Combined stimulation of 4-1BB and CD3 resulted in an enhanced CAT activity compared with CD3 stimulation alone. Thus, 4-1BB may be involved in the activation of HIV-1 replication from latently infected CD4+ T cells.
Wang
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S
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA.
Kim
Y J
YJ
Bick
C
C
Kim
S H
SH
Kwon
B S
BS
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D015500:Chloramphenicol O-Acetyltransferase; D054303:HIV Reverse Transcriptase