Generation of CD28(-) cells from long-term-stimulated CD8(+)CD28(+) T cells: a possible mechanism accounting for the increased number of CD8(+)CD28(-) T cells in HIV-1-infected patients

According to CD28 molecule expression, CD8(+) T cells can be classed as CD2 8(bright), CD28(dim), and CD28(-). The CD28(dim) T cells were found to deri ve from nlitogenic stimulated CD28(-) T cells but also from CD28(bright) T cells through a mechanism of CD28 down-modulation. Moreover, after prolonge d in vitro interleukin-2 stimulation, clonal CD28(bright) cells showed a CD 28(dim) expression before further evolution to a stable CD28(-) phenotype, This loss was concomitant with the disappearance of CD28 mRNA. A study of t he cytokine production pattern revealed that CD28(dim) and CD28- T cell clo nes produced similar levels of type 1 and type 2 cytokines, which differed from those produced by the CD28(bright) T cell clones. A high percentage of CD28(dim) and CD28(-) cells, with similarities in their cytokine productio n pattern, were found in the blood samples of HIV-infected patients, as com pared to healthy donors. The CD28 down-modulation may account for the incre ased number of CD8(+)CD28(-) T cells in HIV-infected patients.