Costimulatory signalling potential of murine MHC class II‐positive T‐clone cells

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Abstract
Activated human and rat T cells as well as mouse T‐cell clones have been reported to synthesize and express major histocompatibility complex (MHC) class II molecules. However, the capacity of class II+ antigen (Ag) presenting T cells to induce proliferation of Ag‐specific cloned T cells has been controversial. We analysed whether the failure of some T‐cell clones to proliferate in response to Ag presented by class II+ T cells is because of a lack of costimulatory cytokine production by the antigen‐presenting cells (APC). As a model system the mouse class II+ cloned BI/O4.1 T cells were used as APC in order to activate the T cell clone KIII5. This T‐helper 1 (Th1) type, GAT (synthetic copolymer of L‐glutamic acid, L‐alanine and L‐tyrosine)‐specific clone is characterized by an efficient downregulation of interleukin‐2 receptor (IL‐2R) with time following antigenic stimulation. KIII5 cells respond to GAT‐presenting splenic antigen‐presenting cells (APC) by IL‐2 production, IL‐2R upregulation and proliferation. When BI/O4.1 T cells were used as APC, KIII5 cells produced IL‐2, but did not proliferate. Reverse transcriptase–polymerase chain reaction (RT–PCR) revealed a lack of IL‐12 production by BI/O4.1 cells. Addition of IL‐12 to a coculture of Ag‐presenting BI/O4.1 cells and KIII5 cells fully reconstituted a proliferative response. IL‐12 in synergy with IL‐2 upregulated IL‐2Rα chain expression and enhanced proliferation of KIII5 cells. Our data suggest, that class II+ T cells are not functional in inducing Ag‐mediated expansion of resting Th1 cells owing to their failure to produce IL‐12, but rather that they play a role in amplification loops during an ongoing immune response.