Research Interests:

Naïve and memory T cells. 

A primary interest of the Jameson lab is studying the responses and maintenance of naïve and memory T lymphocytes.  Naïve T cells (which have not yet undergone immune activation) are typically less effective than memory cells (which, usually, have gone through immune activation) in their response to antigens and their capacity to mediate protective immunity, such as elimination of a pathogen.  Naïve T cells must be maintained, physically and functionally, in readiness for potential antigen encounter.  We're interested in how cytokines (especially IL-7) and the T cell receptor (TCR) interaction with self-MHC molecules induce naïve T cell survival and “tune” their functional reactivity.  Memory T cells are also influenced by environmental factors, and a long term focus has been the cytokine IL-15, which supports memory CD8 T cell maintenance.  In addition, we are interested in how other cytokines and various transcription factors (including Blimp and Bcl-6) dictate whether activated T cells will become long-lived memory cells or short-lived effector cells. 

We also study how memory cells are generated without a typical immune responses.  Lymphopenia (a deficiency of lymphocytes) can cause T cells to proliferate, as if to fill up the empty T-cell “space”.  Interestingly, this process also causes naïve T cells to acquire the phenotype and function of memory T cells, including a much improved ability to offer protective immunity.  Recent studies show that these “homeostatic” memory T cells are present in normal, unimmunized mice.  The presence of such cells leads to the rather surprising prediction that a normal “primary” immune response actually involves participation by both naïve and “memory” T cells, something we’re currently investigating.  We also study factors which influence the T cell response to lymphopenia (including IL-15, TGF-b and TCR encounter with “self” antigens). 

Epicutaneous immunization approaches

A different focus of the lab has been generating protective T cell memory using simplified vaccination approaches.  We’ve developed an approach involving vaccination through the unbroken skin (transdermal, or epicutanous immunization).  Cholera toxin has proven to be a remarkably effective adjuvant for this approach, priming memory CD8 T cells which are capable of protection against bacterial infection.  Current studies focus on how cholera toxin acts as an adjuvant, since it does not appear to require the pathways (such as TLRs) induced by many classic adjuvants. 

The function of Kruppel-like transcription factors in lymphocytes

We are also interested in the function of a family of transcription factors, the Kruppel-like factors (KLF), in T and B cells.  A main focus has been on KLF2 (also called LKLF).  Our analysis of T cells revealed a key role for the factor KLF2 in expression of molecules required for T cell trafficking – i.e. migration throughout the body.  We are now investigating the heterogeneity in KLF2 expression among T cell subsets from various anatomical sites, and how these changes in KLF2 expression influences T cell function.  Interestingly, KLF2 appears to have a quite distinct role in B cells, where it regulates the representation of certain B cell subsets (Marginal Zone and B1 B cells). 

Techniques:

Cellular immunology assays (e.g. T cell activation assays, flow cytometric analysis, cellular adoptive transfer, bone marrow and fetal liver chimeras) and molecular biology techniques (e.g. real time RT-PCR, western blot, generation of transgenic and gene knockout mice) are used extensively in this research.

Selected Recent Publications:

• Sandau, M. M., J. E. Kohlmeier, D. L. Woodland and S. C. Jameson.  (2010)  IL-15 regulates both quantitative and qualitative features of the memory CD8 T cell pool.  J.Immunol. 184:35-44.
• Takada, K. and S.C. Jameson  (2009)  Naïve T cell homeostasis:  From awareness of space to a sense of place.  Nat. Rev. Imm.  9:823-832
• Masopust, D. and S.C. Jameson  (2009)  Memory T cell diversity:  An embarrassment of riches.  Immunity  31:859-871
• Takada, K. and S.C. Jameson.  (2009)  Self Class I MHC molecules support survival of naïve CD8+ T cells but depress their functional sensitivity through regulation of CD8 expression levels. J.Exp.Med.  206:2253-2269
• Weinreich, M.A., K. Takada, C. Skon, S.L. Reiner, S.C. Jameson*, and K.A. Hogquist*  (2009) KLF2 deficiency in T cells results in unrestrained cytokine production and bystander chemokine receptor upregulation. Immunity 31:122-130.  (*Co-corresponding authors).
• Haluszczak, C., A.D. Akue, S.E. Hamilton, L.D.S. Johnson, L.Pujanauski, L. Teodorovic, S.C. Jameson* and R.M. Kedl*  (2009)  The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion.   J.Exp.Med. 206:435-448
• Hamilton, S.E. and S.C. Jameson.  (2008)  The Nature of the Lymphopenic Environment Dictates Protective Function of Homeostatic-Memory CD8+ T Cells. Proc. Natl. Acad. Sci. (USA).  105:18484-18489

• Xiao, Z., M.F. Mescher and S.C. Jameson.  (2007)  Detuning CD8 T cells:  down regulation of CD8 expression, tetramer binding and response during CTL activation.  J.Exp.Med.  204:2667-2677
• Sandau M.M., C.J. Winstead and S.C. Jameson.  (2007)  IL-15 is required for sustained lymphopenia-driven proliferation and accumulation of CD8 T cells.  J. Immunol.  179:120-125
• Carlson C.M., Endrizzi B.T., Wu J., Ding X., Weinreich M.A., Walsh E.R., Wani M.A., Lingrel J.B., Hogquist K.A., Jameson S.C.  (2006).  Kruppel-like factor 2 regulates thymocyte and T-cell migration.  Nature. 442:299-302.
• Hamilton S.E., M.C. Wolkers, S.P. Schoenberger and S.C. Jameson (2006). The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. Nat Immunol. 7:475-481