Cytotoxic T Lymphocyte Response Against SARS-CoV

Our data show that heat-inactivated SARS-CoV is able to induce specific cytotoxic T lymphocyte (CTL) responses in HLA-A2.1/K~b transgenic mice and in peripheral blood mononuclear cells (PBMCs) from healthy HLA-A*0201-matched human donors although repeated challenges with virus-pulsed dendritic cells are required. SARS-CoV-specific CTLs with strong activity against the SARS-CoV-labeled target cells can be visualized by HLA-A*0201/SSp-1 tetramer staining and functionally detected by IFN-γ ELISPOT and cytotoxic assays. We also have found that heat-inactivated SARS-CoV elicited CTL recall responses in peripheral blood of all HLA-A*0201~+ recovered SARS patients over 1 year post-infection, with antigen-specific CTLs sharing a differentiated effector CTL phenotype, CD45RA~+ CCR7~- CD62L~- , and expressing CCR5 and CD44. Intriguingly, heat-inactivated SARS-CoV elicits CTL recall-like responses in 5 of 36 (13.8%) HLA-A*0201~+ healthy donors with no contact history with SARS-CoV, with the CTLs sharing the same phenotypes but exhibiting impaired biofunctions. These results indicate that SARS-CoV infection induces strong and long-lasting CTL-mediated immunity in surviving SARS patients and that cross-reactive memory T cells to SARS-CoV may exist in T cell repertoire of a small subset of healthy individuals with no contact history with SARS-CoV and can be reactivated by SARS-CoV infection. This study would greatly help in characterizing mechanisms of virus control and immunopathology in SARS-CoV infection and the development of prophylactic and therapeutic strategies against this lethal respiratory disease.