Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4⁺ T cells

Activation of CD4⁺ T lymphocytes from human immunodeficiency virus- type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage- tropic HIV-1. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1- resistant phenotype similar to that seen in some highly exposed and HIV- uninfected individuals.