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 responsiveness to stimulation with anti-CD3/CD28-coated beads, as surrogate antigen-presenting cells. While the CD4+ subset responded with sustained proliferation, 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-xL expression. The CD8+ but not the CD4+ subset developed a reversible double-positive phenotype during CD28 costimulation. This finding may have some bearing on the appearance of double-positive T-cells in human peripheral blood. This double-positive subset was shown to undergo a statistically significantly increase during aging in humans. Taken together, the above data have important implications for immunotherapy and immune senescence.