Human immunodeficiency virus type 1 replication, immune activation, and circulating cytotoxic T cells against uninfected CD4(+) T cells

Cytotoxic T lymphocytes (CTL) that kill uninfected activated CD4(+) T cells can be induced in vitro by stimulating CD8(+) T cells with activated autol ogous CD4(+) T cells. Similar CTL have been detected in circulating T cells from human immunodeficiency virus type 1 (HIV)-infected individuals. To de fine the in vivo correlates of this CTL activity, we studied plasma beta-2 microglobulin and HIV RNA levels, T-lymphocyte subset counts, and expressio n of CD28 on CD8(+) T cells concurrently with circulating CTL activity agai nst uninfected CD4(+) T cells in 75 HIV-infected individuals at different s tages of disease progression. Mean values of each parameter were compared i n subsets of this group of 75 segregated on the basis of this CTL activity. The group with CTL against uninfected activated CD4(+) T lymphocytes had m ore CD8(+) T cells, a higher percentage of CD28(-) CD8(+) T cells, and high er plasma levels of HIV RNA and beta-2 microglobulin. CTL against uninfecte d activated CD4(+) T cells were predominantly CD28(-) and in HIV-infected i ndividuals were associated with immunological or virological evidence of pr ogressive disease. In HIV infection, circulating CTL activity against uninf ected activated CD4(+) T lymphocytes is associated with immune activation, CD8(+) T cell expansion, accumulation of CD28(-) CD8(+) T cells, and inadeq uate suppression of HIV replication.