Impact of V beta 8+/+ T cells on the development of increased airway reactivity and IgE production in SJL mice.

SJL mice have been extensively characterized as "low-responder" animals in terms of IgE-dependent immediate-type hypersensitivity responses. Since these mice are genetically deficient in certain TCR Vbeta gene segments, we asked whether this might be the reason for the "low-responder" status. Specifically in H-2d mice the TCR-Vbeta8.2 gene element has been shown to play an important role in Th2 immune responses to ovalbumin (OVA). Utilizing a TCR Vbeta8. 2-transgenic SJL (SJL Vbeta8+/+) mouse, we examined whether the H-2s -bearing "low-responder" mouse could be converted into a "high-responder" animal. Remarkably, non-sensitized SJL Vbeta8+/+ mice demonstrated strongly elevated levels of total IgE antibody. Mitogen-stimulated T cells from these mice released high amounts of IL-4 as compared to SJL wild-type (wt) mice. In addition, sensitization to OVA via the airways resulted in the development of increased airway responsiveness in SJL Vbeta8+/+ mice, but not in SJL wt animals. The results indicate that the capacity to produce IgE and IL-4 and to develop increased airway responsiveness can be restored in SJL wt mice by introducing the Vbeta8.2 gene segment into the TCR repertoire.