Colleen Winstead

E-mail: wins0022@umn.edu

Thesis Advisor: Alex Khoruts

Year entered: 2004

Degrees received:
B.S., Biology, Marquette University, Milwaukee, WI 1997
M.S., Zoology, Miami University, Oxford, OH 2001

Honors and Awards:

• DOVE Fellowship 2004
• R01 Research Supplement for Underrepresented Minorities (PA-01-079)
• AAI Mentor/Minority Trainee Travel Award

Thesis research:
T cell diversity is a key feature of the adaptive immune system. Lymphopenia-induced proliferation (LIP) can trigger oligoclonal expansion of T cells reacting to foreign or self-antigens. This can result in loss of T cell diversity and compromise immune fitness that can be achieved following reconstitution by LIP. We have demonstrated that CD4+CD25+Fopx3+ regulatory T cells (Tregs) selectively inhibit the spontaneous (fast) form of LIP, which is associated with differentiation into memory/effector-like cells, and is likely to contain the most reactive T cell clones. Selective suppression of these clones is likely to leave more resources for T cells undergoing the slower homeostatic form of LIP (Winstead et al. 2008 JI 108: 7305). Our current hypothesis is that one of the functions of Tregs is to maintain the T cell diversity and overall immune fitness during reconstitution from lymphopenia. Structural data generated using flow cytometric analysis of TCR Vbeta usage and PCR-based TCR Jbeta spectratyping suggest Tregs effectively prevent the emergence of 'holes' in the T cell repertoire following LIP. We are currently testing the functional consequences of LIP in the presence or absence of Tregs through sampling and phenotyping of antigen specific cells by means of magnetic bead pull-down with MHC class I and II tetramers.

Publications:

• Winstead CJ, Fraser JM, Khoruts A. 2008. Regulatory CD4+CD25+Foxp3+ T
  cells selectively inhibit the spontaneous form of lymphopenia-induced proliferation of naïve T cells. J. Immunol. 180(11): 7305-17.

• Sandau MM, Winstead CJ, Jameson SC. 2007. IL-15 is required for sustained
  lymphopenia-driven proliferation and accumulation of CD8 T cells. J. Immunol.
  179(1): 120-5.