MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED CD8(-CELLS AND CLASS II-RESTRICTED CD4(+) T-CELLS, RESPECTIVELY, MEDIATE AND REGULATE CONTACT SENSITIVITY TO DINITROFLUOROBENZENE() T)

Contact sensitivity (CS) is a form of delayed-type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like cl assical delayed-type hypersensitivity responses, by CD4(+) Thelper-1 c ells. The aim of this study was to identify the effector T cells invol ved in CS. We studied CS to the strongly sensitizing hapten dinitroflu orobenzene (DNFB) in mice rendered deficient by homologous recombinati on in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8(), CD4(+), or both, T cells. MHC class I single-deficient and MHC clas s I/class II double-deficient mice, both of which have a drastic reduc tion in the number of CD8(+) T cells, were unable to mount a CS respon se to DNFB. In contrast, both MHC class II-deficient mice and normal m ice treated with an anti-CD4 monoclonal antibody (mAb) developed exagg erated and persistent responses relative to heterozygous control litte rmates. Furthermore, anti-CD8 mAb depletion of class II-deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4(+) T cells in class II-deficient mice by anti-CD4, mAb treatment did not diminish the intensity of CS. These d ata clearly demonstrate that class I-restricted CD8(+) T cells are suf ficient for the induction of CS to DNFB, and further support the idea that MHC class II-restricted CD4(+) T cells down-regulate this inflamm atory response.