Response differences between human CD4+ and CD8+ T-cells during CD28 costimulation: Implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging

Since CD28 costimulation is critical for T-cell activation, there is great interest in CD28 as a target for immuntherapeutic approaches. We show that stimulation of human CD4(+) and CD8(+) T-cells differs in their responsiven ess to stimulation with anti-CD3/CD28-coated beads, as surrogate antigen-pr esenting cells. While the CD4(+) subset responded with sustained proliferat ion, CD8(+) T-cells grew for a limited period only and failed to produce IL -2 beyond the first few days in culture. This decrease is accompanied with an increased rate of apoptosis in CD8(+) T-cells despite Bcl-x(L) expressio n. The CD8(+) but not the CD4(+) subset developed a reversible double-posit ive phenotype during CD28 costimulation. This finding may have some bearing on the appearance of double-positive T-cells in human peripheral blood. Th is double-positive subset was shown to undergo a statistically significantl y increase during aging in humans. Taken together, the above data have impo rtant implications for immunotherapy and immune senescence, (C) 2000 Academ ic Press.