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

Previous analysis of systemic adaptive immune responses had shown that MVA vaccination elicits strong CD8+ and CD4+ T cell responses with a T-helper type 1 (Th1)-dominant profile [25, 30, 67, 68] as well as orthopoxvirus-specific antibodies [25, 68, 69] . Here we demonstrate that antigen-specific immune responses can be detected in the respiratory tract at early times after immunization. Of note, we found two to three-times higher numbers of IFN-y producing VACV (B8R [20] [21] [22] [23] [24] [25] [26] [27] ) specific CD8+ T cells in lungs than in spleens. This supports the hypothesis that early local priming of antigen-specific T cells may occur, which is possibly associated with MVA-induced formation of bronchusassociated lymphoid tissue [45] . The rapid expansion of virusspecific CD8+ T cells is further supported by the recent finding of Chaudhri and coworkers that antigen-specific T cell receptors can be transferred and shared among CD8+ T cells to enhance the anti-viral response upon orthopoxvirus infection [70] .