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.
Gautam
S C
SC
Department of Immunology, Cleveland Clinic Foundation, OH 44106.
Battisto
J R
JR
D000284:Administration, Oral; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003864:Depression, Chemical; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D008808:Mice, Inbred CBA / Q000276:immunology; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*
D006241:Haptens; D010853:Picryl Chloride