Priming antiviral cytotoxic T lymphocytes: requirement for CD4+ cells is dependent on the antigen presenting cell in vivo.
We have analyzed cytotoxic thymus-derived lymphocyte (CTL) responses to vesicular stomatitis virus (VSV) to determine whether VSV precursor CTL (pCTL) can be primed in vivo in the absence of CD4+ cells. Our studies demonstrated that secondary anti-VSV CTL responses in vitro were markedly reduced by CD4-depletion prior to priming in vivo with VSV. Limiting dilution analysis indicated that the vast majority (> 90%) of VSV pCTL failed to become primed when exposed to VSV in the absence of CD4+ cells. A second minor population (5-10%) of pCTL was identified that was reproducibly primed in CD4-deficient mice. In contrast to CD4-depleted mice infected with free, infectious virus, CD4-deficient mice primed with VSV-infected, activated B cells mounted normal secondary anti-VSV CTL responses in vitro. Precursor estimates indicated that virtually all VSV pCTL became primed using this cellular immunogen. CD4-independent priming could not be achieved using VSV-infected, activated T cells, another permissive cell type for VSV replication. Thus, most VSV pCTL require inductive signals from classical CD4+ helper T cells in order to become primed in vivo and this requirement may be regulated in vivo by the antigen presenting cell.
Ciavarra
R P
RP
Department of Microbiology, Eastern Virginia Medical School, Norfolk 23501.
Tedeschi
B
B
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000911:Antibodies, Monoclonal