T cell immunity and cytokine receptor signaling

Project: Research project

Project Details


The processes by which activated T cells develop into armed effector cells or ultimately persist
as long-lived memory cells are becoming better understood. Signal transduction through the IL-
2R prominently contributes to these processes. IL-2 promotes optimal T effector responses and
is essential for extensive effector cell proliferation and development in vitro. Furthermore, recent
data suggest that IL-2 signaling during the primary response may be critical for memory CD8 T
cells to proliferate and mediate effector activity upon a recall antigenic challenge. Nevertheless,
the molecular mechanism that regulates effector versus memory programming and the precise
contribution by IL-2 to these processes remains largely undefined. During our last grant period,
we developed a culture system that models effector and memory T cell development and
characterized unique mouse models with selective defects in IL-2R signaling by peripheral T
cells. These experimental tools are especially useful for direct analysis of IL-2-dependent
molecular events controlling effector and memory programming. Utilizing these, we uncovered a
novel auto-regulatory loop in which IL-2 inhibits its own production that may be an important
checkpoint for effector and/or memory production. This inhibitory pathway depends upon the
transcriptional repressor Blimp-1.Thus, the major objectives for this proposal are to establish the
molecular basis by which IL-2 signaling regulates effector and memory cell programming and to
ascertain the biological relevance of Blimp-1-dependent regulation of activated T cells. The
specific aims are: 1) To investigate how IL-2R[unreadable] signaling regulates individual down-stream
molecular targets in activated CD4 and CD8 T cells;2) to determine the relevance of IL-2R[unreadable]
signaling during the development of immune responses in vivo to nominal antigen and infectious
agents;and 3) to directly evaluate the function of IL-2-dependent Blimp-1 in T cell immune
Effective start/end date9/26/088/31/10


  • National Institute of Allergy and Infectious Diseases: $382,500.00
  • National Institute of Allergy and Infectious Diseases: $382,500.00


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