Feeding trinitrochlorobenzene inhibits development of hapten-specific cytotoxic T lymphocytes by interfering with helper T-cell function.

The development of hapten-specific cytotoxic T lymphocytes (CTLs) in mice that were made tolerant by administering the hapten trinitrochlorobenzene (TNCB) intragastrically was examined. The generation of CTL specific for hapten-modified self-antigens in vivo was reduced in animals fed TNCB three times at weekly intervals prior to immunization for CTLs. In addition, splenic cells from hapten-fed mice were unable to develop CTLs in vitro. The inhibition of CTL formation was strictly trinitrophenyl-self-specific as responses to fluorescein isothiocyanate-self- or allogeneic stimulators were fully developed. Limiting dilution analyses revealed that the lack of development of CTL in hapten-fed mice was not attributable to a diminution in the frequency of precursor CTL specific for hapten altered self-antigen. By contrast, the inability of spleen cells of hapten-fed mice to produce CTLs in vitro was reversed by incorporating Lyt1+ cells from normal mice or preformed helper lymphokines into culture. That the nonresponsivity in hapten-fed mice was attributable to nonfunctioning helper cells became additionally evident when splenic L3T4+ cells from hapten-fed mice, in contrast to those from normal mice, were found to be unable to assist normal Lyt2+ splenic cells develop hapten-specific CTLs. Furthermore, fed-L3T4+ cells were ruled out to be directly suppressive of CTL production. This work illustrates that hapten-specific helper T-cell function becomes defective following orally administered hapten and that this deficit contributes to suppression of hapten-specific CTL production.