title: 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.
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.
authors.affiliation: Division of Clinical Immunology and Allergy, UCLA, Los Angeles, California, 90095, USA.
authors.forename: I
authors.initials: I
authors.lastname: Laux
authors.forename: A
authors.initials: A
authors.lastname: Khoshnan
authors.forename: C
authors.initials: C
authors.lastname: Tindell
authors.forename: D
authors.initials: D
authors.lastname: Bae
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: R B
authors.initials: RB
authors.lastname: Effros
authors.forename: A
authors.initials: A
authors.lastname: Nel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology; D018106:CD28 Antigens / Q000276:immunology* / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006682:HLA-DP Antigens / Q000097:blood / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype
chemical_list: D018106:CD28 Antigens; D006682:HLA-DP Antigens