Lisa Johnson

E-mail: joh01715@umn.edu

Thesis Advisor: Steve Jameson

Year entered: 2004

Degrees received:
B.S., Biology/Biotechnology, Carleton University, Ottawa, Ontario, Canada 2000

Thesis research:
The cytokines that positively modulate homeostatic proliferation (IL-2, IL-7, and IL-15) are relatively well understood. It is not clear how CD8+ homeostatic proliferation is negatively regulated. We have investigated the role of tumor growth factor beta (TGF-beta) in generating CD8+ T cell memory through homeostatic proliferation and conventional antigen priming with recombinant Listeria monocytogenes expressing ovalbumin (LM-OVA). Lack of TGF-beta signaling on T cells has been demonstrated to have catastrophic effects in the steady state as indicated by defective thymic development and presence of activated cells in the periphery. Using mice that express a dominant negative form of the TGF-beta RII under the control of the CD2 promoter (RII DN), we have shown that naive OT-I RII DN have greater homeostatic proliferative capacity as compared to their wild type counterparts. Even as new thymic output re-fills peripheral lymphoid organs over time, OT-I RII DN continue to divide suggesting that TGF-beta signaling on CD8+ is involved in sensing lymphoid space and controlling expansion. In contrast to lymphopenia induced proliferation, OT-I wt and OT-I RII DN transferred into wild-type hosts and challenged with LM-OVA have similar expansion kinetics, with only a slight increase in OT-I RII DN at the peak of the response. This indicates that TGF-beta is a negative regulator of homeostatic proliferation, but that lack of TGF-beta signaling may not be advantageous in generating memory cells in an antigen driven response.

Publications:

• Modiano, J.F., L.D.S. Johnson, and D. Bellgrau. 2008. Negative Regulators in homeostasis of naïve peripheral T cells. Immunologic Research. (online April 15, 2008)

• Haluszczak, C., A.D. Akue, S.E. Hamilton, L. Pujanauski, L. Teodorovic, L.D.S. Johnson, S.C. Jameson, and R.M. Kedl. 2008. The naïve CD8+ T cell pool contains a variable frequency of memory phenotype T cells bearing the signature of homeostatic expansion. (submitted)