Separation of CD4+ functional responses by peptide dose in Th1 and Th2 subsets expressing the same transgenic antigen...

CD4+ T cells from alpha beta-TCR transgenic mice were used to explore the effect of antigen dose on various functional activities. This transgenic system provides for a source of antigen-specific T cells with the same TCR which can develop into Th1 and Th2 phenotypes under controlled conditions. Of particular interest was to determine if detachment of adherent targets from their substrate could be separated from other functional activities by either antigen dose or functional subset. Using this model, we have found that (a) Th1 and Th2 phenotypes exhibit a similar peptide dose-dependent pattern of detachment and lysis, although Th2 are generally less lytic on both fibroblast and lymphoma targets; (b) detachment and lysis can be dissociated from cytokine production by low peptide doses; (c) detachment and lysis can be physiologically as well as temporally and pharmacologically uncoupled as most targets recovered after detachment by Th2 effectors retain their capacity to proliferate.