CD4+ T cell-mediated killing of major histocompatibility complex class II-positive antigen-presenting cells (APC). III. CD4+ cytotoxic T cells induce apoptosis of APC.
A subset of CD4+ T cells, belonging to the T helper type 1 (Th1) cells, kills antigen-presenting cells (APC) in an antigen-specific and major histocompatibility (MHC) class II-restricted way. Evidence is presented that CD4+ cytotoxic T lymphocytes (CTL) induce apoptosis or programmed cell death within susceptible APC as witnessed by quantitative DNA fragmentation. Apoptosis is more reliable to determine cell death than the 51Cr-release assay, because some cells demonstrate resistance to CD4-mediated lysis in the 51Cr-release assay. Apoptosis becomes manifest after 2 to 4 h of incubation preceding the disintegration of the target cells which is detectable between 12 and 24 h as measured by the 51Cr-release assay. Unstimulated B cells, which are not killed, but function as APC, do not undergo apoptosis, whereas lipopolysaccharide or anti-mu-activated B cell blasts show apoptosis and are efficiently lysed. Several CD4+ Th2-type cells tested, which did not demonstrate killing of APC as measured by the 51Cr-release assay, are unable to mediate programmed cell death of appropriate APC. Actinomycin D or cycloheximide, inhibitors of transcription and translation, respectively, fail to prevent apoptosis of APC excluding the involvement of newly synthesized soluble products as mediators of killing. Pretreatment of CD4+ CTL, but not of APC with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a specific inhibitor of the anion transport, efficiently prevents apoptosis of APC, although the secretion of interleukins is not affected. We propose, that upon contact of the CD4+ CTL with APC, molecules of yet undefined nature are activated and released in a polar fashion at the contact site and induce the endogenous pathway of programmed cell death.
Grogg
D
D
Institute for Medical Microbiology, University of Basel, Switzerland.
Hahn
S
S
Erb
P
P
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D004247:DNA; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid