Specific epitope‐induced conversion of CD8+memory cells into effector cytotoxic T lymphocytesin vitro:presentation of peptide antigen by CD8+T cells

摘要

AbstractThe requirements for the conversion of CD8+memory T cells into effector class I major histocompatibility complex (MHC) Kd−restricted cytotoxic T (Tc) cellsin vitrohave been studied. Purified CD8+splenocytes from influenza A/WSN‐primed BALB/c (H‐2d) mice stimulated with a synthetic nucleoprotein peptide 147–158 R156−(NPP) alone generated Tccells specific for influenza virus‐infected target cells. No additional requirements for accessory cells or their lymphokine products were necessary indicating that peptide antigen (Ag) in association with Kdwas presented on CD8+T cells. The evidence for presentation of NPP by CD8+T cells was supported by the use of CD8+memory T cells from semiallogeneic bone marrow radiation chimeras of P1→ F1type (H2b→ H‐2dx H‐2bF1). Memory CD8+splenocytes from A/WSN‐immune chimeras did not develop into secondary effector Tccells as a result of a 4‐day culture with NPP alone, however, were able to do so if NPP was presented by Kd−bearing Ag‐presenting cells. In addition, these results exclude the possibility of direct recognition of free NPP molecules by the specificT cell receptor of CD8+memory T cells. CD8+memory splenocytes (H‐2b) from chimeras were also able to develop into functionally active Tccells as a result of presentation of Db−restricted synthetic peptide (NP 366–374) with a sequence derived from influenza virus nucleoprotein with high affinity for DbMHC class I molecules. Blockade of endogenously produced interleukin 2 (IL‐2) activity by anti‐IL‐2 or anti‐IL‐2 receptor monoclonal antibody in the culture of CD8+memory T cells during a 4‐day NPP stimulation completely abolished Tccell generation, indicating that the utilization of this lymphokine is absolutely required for the secondary Tccell development. These findings demonstrate that CD8+memory T cellsper seare able to recognize the restimulating epitope as a result of its presentation by CD8+T cells and develop into cytolytically active and highly specific Tccells with no requirements for other cellular