Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1613-8. doi: 10.1073/pnas.1121307109. Epub 2012 Jan 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / immunology*
  • Humans
  • Immunologic Memory
  • Interleukin-6 / immunology
  • Signal Transduction
  • T-Lymphocyte Subsets*
  • T-Lymphocytes / immunology*
  • Tetraspanin 28 / immunology*


  • CD28 Antigens
  • Interleukin-6
  • Tetraspanin 28