Normal human CD8+ T cell clones were co-isolated from the same culture wells as CD4+ T effector cell clones specific for myelin basic protein (MBP). Microcultures from which the CD8+ clones were isolated initially proliferated weakly to whole MBP and to an MBP peptide spanning residues 90-170. This pattern of response was similar to strongly proliferating wells that yielded CD4+ T cell clones specific for the 90-170 peptide. After repeated stimulation, however, no response to MBP or MBP 90-170 was detected, even though the number of cells increased after stimulation. Phenotyping and TCR analyses revealed the presence of two CD8+ CD4- IL-2R+ T cell isolates that expressed a single Vβ2 gene (Vβ217) that differed from the CD4+ isolates that uniformly expressed Vβ214. One of these CD8+ clones (C9) inhibited the antigen-driven proliferation of an autologous MBP 90-170 reactive clone but not an autologous clone specific for Herpes simplex virus (HSV). without affecting MHC non-resuicted mitogen responses of the same clones. Moreover, C9 did not inhibit heterologous CD4+ T cell clones specific for MBP 1-38 or 90-170. A culture supernatant of the CD8+ clone showed the same pattern but lower levels of inhibition. C9 had mild cytolytic activity when incubated at high ratios with an autologous MBP-specific CD4+ clone. Lysis was blocked completely by anti-MHC class I antibodies. but not by anti-MHC II antibodies. These data suggest that CD8+ T cells can recognize idiotypic determinants on CD4+ MBP-specific T cells, and raise the possibility that CDS+ T cells could participate in the normal regulation of potentially pathogenic autoreactive effector cells.
ASJC Scopus subject areas
- Immunology and Allergy