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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.

I Laux·A Khoshnan·C Tindell·D Bae·X Zhu·C H June·R B Effros·A Nel
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Abstract

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-x(L) 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.

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AdultAgedAged, 80 and overAgingCD28 AntigensCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesHLA-DP AntigensHumansImmunotherapy, AdoptiveLymphocyte ActivationPhenotypeJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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BibTeXRIS

I Laux, A Khoshnan, C Tindell, D Bae, X Zhu, C H June, R B Effros, A Nel. 2000. 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.. https://doi.org/10.1006/clim.2000.4902

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