Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox

Kremer, Melanie; Suezer, Yasemin; Volz, Asisa; Frenz, Theresa; Majzoub, Monir; Hanschmann, Kay-Martin; Lehmann, Michael H.; Kalinke, Ulrich; Sutter, Gerd

To further confirm the relevance of T cell immunity in rapid protection by MVA immunization we adoptively transferred naïve CD3+ splenocytes, which comprise mainly T cells, into RAG-1 2/2 mice. After two days these mice were vaccinated with 10 8 PFU MVA and challenged two days later with ECTV. Indeed, the transfer of T cells prior to vaccination was fully sufficient to protect RAG-1 2/2 mice against lethal infection, whereas control RAG-1 2/2 mice all died despite MVA immunization ( Figure 6 ; P = 0.0003). Interestingly, control RAG-1 2/2 showed a slight delay in onset of disease upon MVA immunization ( Figure 3A, Figure 6 ) which cannot be observed in mice depleted of CD4+ and CD8+ T cells (Figure 4 ). This effect may be due to elevated NK cell numbers in non-lymphoid tissue of RAG-1 2/2 mice [56] that might transiently compensate for the lack of T and B cells.