Journal
CLINICAL IMMUNOLOGY
Volume 96, Issue 3, Pages 187-197Publisher
ACADEMIC PRESS INC
DOI: 10.1006/clim.2000.4902
Keywords
CD28 costimulation; T-lymphocytes; T-cell subsets; double-positive PBL; aging; apoptosis
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Funding
- NATIONAL INSTITUTE ON AGING [P60AG010415, R01AG014992] Funding Source: NIH RePORTER
- NIA NIH HHS [AG10415, AG14992] Funding Source: Medline
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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, (C) 2000 Academic Press.
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