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Original Research ARTICLE

Front. Immunol., 11 February 2011 | http://dx.doi.org/10.3389/fimmu.2011.00004

Differential role of “signal 3” inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo

Nhat-Long L. Pham1, Vladimir P. Badovinac2 and John T. Harty1,3*
  • 1 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
  • 2 Department of Pathology, University of Iowa, Iowa City, IA, USA
  • 3 Department of Microbiology, University of Iowa, Iowa City, IA, USA

Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells.

Keywords: memory CD8 T cells, inflammatory cytokines

Citation: Pham N-LL, Badovinac VP and Harty JT (2011) Differential role of “signal 3” inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. Front. Immun. 2:4. doi: 10.3389/fimmu.2011.00004

Received: 09 November 2010; Paper pending published: 06 December 2010;
Accepted: 28 January 2011; Published online: 11 February 2011.

Edited by:

Bruce Reinhold, Dana-Farber Cancer Institute, USA

Reviewed by:

Leo Lefrancois, University of Connecticut Health Center, USA
Jonathan Duke-Cohan, Dana-Farber Cancer Institute, USA
Bo Zhou, Dana-Farber Cancer Institute, USA

Copyright: © 2011 Pham, Badovinac and Harty. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: John T. Harty, Department of Microbiology, Department of Pathology, and Interdisciplinary Program in Immunology, University of Iowa, 3-530 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USA.e-mail: john-harty@uiowa.edu