Human CD81 directly enhances Th1 and Th2 cell activation, but preferentially induces proliferation of Th2 cells upon long-term stimulation.
BACKGROUND
CD81, a cell-surface protein of the tetraspanin superfamily, has been shown to costimulate T cell activation in murine T cells, and is involved in development of Th2 immune responses in mice.


RESULTS
Here it is shown that stimulation of CD81 on human T cells can enhance T cell activation by antigen or superantigen, causing an increase in the early activation marker CD69, and increasing the number of cytokine-producing and proliferating T cells. Interestingly, CD81 costimulates cytokine production by T cells producing both Th1 and Th2 cytokines. Although human CD81 is highly expressed on non-T as well as T cells, CD81 costimulation appears to act directly on T cells. Pre-incubation of purified T cells with anti-CD81 antibody is sufficient to increase T cell activation, while pre-incubation of non-T cells is not. However, long-term polyclonal stimulation of T cells by anti-CD3 antibody, in the presence of CD81 costimulation, biases T cells towards the production of IL-4 and not IFNgamma. This is accomplished by a preferential proliferation of IL-4-producing cells.


CONCLUSIONS
Thus, signalling through CD81 on T cells costimulates both Th1 and Th2 cells, but increases the number of Th2 cells during long-term activation.
Maecker
Holden T
HT
BD Biosciences, Immunocytometry Systems, 2350 Qume Drive, San Jose, CA 95131, USA. holden_maecker@bd.com
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D003432:Cross-Linking Reagents / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D060225:Tetraspanin 28; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000099192:CD69 Antigens
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D016207:Cytokines; D007376:Interleukin-2; D037181:Lectins, C-Type; D008565:Membrane Proteins; D060225:Tetraspanin 28; D000099192:CD69 Antigens; C554798:CD81 protein, human; C554799:Cd81 protein, mouse