Expansion of rare CD8(+)CD28(-)CD11b(-) T cells with impaired effector functions in HIV-1-infected patients

The decline in the number of CD4(+) T cells in HIV-l-infected patients is k nown to be related to the increased number of CD8(+)CD28(-) T cells. In thi s paper, we show that CD8(+)CD28(-) T cells from HIV-positive patients have an impaired capability to interact with human endothelial cells. This is d ue to the dramatic expansion, within this subset, of rare CD11b(-) cells la cking cell-cell adhesion functions. In 50 HIV-positive patients, 19.5% +/- 6.5% of all T cells were CD8(+)CD28(-)CD11b(-), whereas only 0.8% +/- 0.4% of all T cells from healthy donors showed this uncommon phenotype. The perc entage of circulating CD8(+)CD28(-)CD11b(-) T cells was strongly related to the percentage of CD4(+) T cells (r = -0.82). This population is peculiar in terms of HIV infection and was found to possess some characteristics ass ociated with effector functions but its cytotoxic properties were impaired. The percentage of target cells lysed by CD8(+)CD28(-)CD11b(-) was signific antly lower than that of cells lysed by its CD11b(-) counterpart (p <.05) b oth at low (5:1) or at relatively high (20:1) effector/target ratios. CD8()CD28(-)CD11b(-) T cells, which lack the ability to interact with endotheli al cells, are likely to accumulate and persist in circulation. The biologic properties of CD8(+)CD28(-)CD11b(-) T cells suggest that these cells might be endstage or aberrant differentiated effector cells. Lack of cell-cell a dhesion and impaired cytolytic functions favor the hypothesis of a role for CD8(+)CD28(-)CD11b(-) T cells in the development of immunodeficiency.