Th cells and Th2 responses can develop in the absence of MHC class II-CD4 interactions

In this paper, me address the question whether CD4 and MHC class II express ion are necessary for the development of the T helper lineage during thymoc yte maturation and for activation-induced Th2 responses. To bypass the CD4- MHC class II interaction requirements for positive selection and activation , we used mice that are doubly transgenic for CD8 and for the MHC class I-r estricted TCR F5, This transgene combination leads to MHC class I-dependent maturation of CD4 lineage cells. Upon activation, these CD4 lineage T cell s secrete IL-4 and give help to B cells but show no cytotoxic activity. Rem arkably, neither MHC class II nor CD4 expression are necessary for the gene ration and helper functions of these cells. This suggests that under normal conditions, coreceptor-MHC interactions are necessary to ensure the canoni cal combinations of coreceptor and function in developing thymocytes, but t hat they do not determine functional commitment. Our results also imply tha t expression of the CD4 gene does not influence, but is merely associated w ith the decision to establish the T helper program. In addition, we show th at activation through TCR-MHC class I interactions can induce Th2 responses independently of CD4 and MHC class II expression.