Route and CD4 help requirements: In a comparison of LCMV (i.v.), a virus-like particle infection expressing LCMV antigen gp33–41 (s.c.), and VACV engineered to express LCMV antigen gp33–41 (i.p.), the primary antigen-specific CD8+ T cell response for LCMV gp33–41 peptide was found to be independent of CD4+ T cell help, except in the case of i.p. vaccinia infection. The gene discussed is CD4; the disease is infection.