SPECIFIC TOLERIZATION OF ACTIVE CYTOLYTIC T-LYMPHOCYTE RESPONSES IN-VIVO WITH SOLUBLE PEPTIDES

A promising approach toward preventing and treating autoimmune disease involves identifying the mediating antigen and then tolerizing the au toreactive T cells with the corresponding antigen. For success, this m ethod will require the specific tolerization of active helper or CTL r esponses while maintaining the integrity of the immune system. In this report, we selectively eliminated an ongoing CTL response by administ ering soluble peptide. BALB/c mice were immunized with two H-2K(d)-res tricted immunodominant CTL epitopes derived from HIV and malaria toget her with a T helper epitope to elicit a strong CTL response. Beginning 3 days later, mice were injected 3 times at 3-day intervals with 500 mu g of only one or both of these epitopes in PBS. Following these inj ections, only one of two active CTL responses was tolerized without af fecting T helper cells. This tolerization state requires antigen for i ts maintenance, may be retolerized upon return, and is not due to acti ve or antigen-driven bystander suppression. This study suggests that s oluble peptides may be utilized to treat or prevent autoimmune disease s caused by autoreactive CTLs. (C) 1996 Academic Press, Inc.