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.