Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81.
Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells: Primary human naïve T cells are better costimulated by CD81, whereas the memory T-cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naïve T cells by CD81 was due to prolonged signal transduction compared with that by CD28. We found that IL-6 played a role in the activation of the naïve T-cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on T-cell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T-cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naïve T cells with their broad repertoire.
Division of Oncology, Department of Medicine, and Division of Immunology and Rheumatology, Stanford University Medical Center, Stanford, CA 94305, USA.
Yael
Y
Sagi
Angela
A
Landrigan
Ronald
R
Levy
Shoshana
S
Levy
D018106:CD28 Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D015850:Interleukin-6 / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*; D060225:Tetraspanin 28 / Q000276:immunology*
D018106:CD28 Antigens; D015850:Interleukin-6; D060225:Tetraspanin 28