Rapid conversion of effector mechanisms from NK to T cells during virus-induced lysis of allogeneic implants in vivo.
Viral infections can strongly stimulate both NK cell and allospecific CD8 T cell responses, and these same effector cells can lyse allogeneic cell lines in vitro. However, the impact of viral infections on the effector systems mediating rejection of allogeneic tissues in vivo has not been fully explored. Using in vivo cytotoxicity assays, we evaluated the effector systems mediating the rejection of CFSE-labeled allogeneic splenocytes after an infection of C57BL/6 (B6) mice with lymphocytic choriomeningitis virus. Naive B6 mice predominantly used a NK cell-effector mechanism to reject allogeneic splenocytes because they rejected BALB/C (H2(d)) splenocytes but not CBA (H2(k)) splenocytes, and the rejection was prevented by immunodepletion of NK1.1(+) or Ly49D(+) NK cells. This rapid and efficient in vivo cytotoxicity assay recapitulated the specificity of NK cell-mediated rejection seen in longer duration in vivo assays. However, as early as 1 day after infection with lymphocytic choriomeningitis virus, a CD8 T cell-dependent mechanism participated in the rejection process and a broader range of tissue haplotypes (e.g., H2(k)) was susceptible. The CD8 T cell-mediated in vivo rejection process was vigorous at a time postinfection (day 3) when NK cell effector functions are peaking, indicating that the effector systems used in vivo differed from those observed with in vitro assays measuring the killing of allogeneic cells. This rapid generation of allospecific CTL activity during a viral infection preceded the peak of viral epitope-specific T cell responses, as detected by in vivo or in vitro cytotoxicity assays.
Brehm
Michael A
MA
Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA.
Daniels
Keith A
KA
Ortaldo
John R
JR
Welsh
Raymond M
RM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006183:H-2 Antigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D008213:Lymphocyte Activation / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D018052:Pichinde virus / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000637:transplantation* / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens