Differences in regulatory pathways identify subgroups of T cell-derived Th2 cytokines.
We analysed regulatory mechanisms involved in the production of Th2 cytokines by freshly isolated human T cells. We used an in vitro culture system in which the primary signal was provided by a cross-linking anti-CD3 MoAb presented on the Fc receptors of P815 cells. Both CD80 and CD86, expressed on transfected P815 cells, were able to provide efficient costimulation for the production of IL-4, IL-5 and IL-13. IL-2 was also highly important for induction of all three Th2 cytokines. However, differences between IL-4 on the one hand and IL-5 and IL-13 on the other hand were observed when sensitivity to cyclosporin A (CsA) was studied. CsA (an inhibitor of calcineurin phosphatase activity) strongly inhibited IL-4 production, but it did either not affect or even increased IL-5 and IL-13 production. In accordance with this, CD80 and phorbol myristate acetate (PMA) (without anti-CD3 or calcium ionophore) were sufficient to induce production of IL-5 and IL-13, but not of IL-4. The subgrouping of Th2 cytokines was further confirmed at another level on the basis of differences in cell sources: IL-4 was predominantly produced by CD4+ T cells, while IL-5 and IL-13 were produced by both CD4+ and CD8+ T cells. Thus, differences in cell sources and in the requirement of the calcium/calcineurin-signalling pathway allowed us to identify two subgroups (IL-4 and IL-5/IL-13) among human Th2-type T cell cytokines.
Rafiq
K
K
Laboratory of Experimental Immunology and Division of Paediatrics, Catholic University of Leuven, Leuven, Belgium.
Bullens
D M
DM
Kasran
A
A
Lorré
K
K
Ceuppens
J L
JL
Van Gool
S W
SW
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018793:Interleukin-13 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D016572:Cyclosporine; D002118:Calcium