EGR-2 Is Not Required for In Vivo CD4 T Cell Mediated Immune Responses

Background: The zinc finger transcription factor EGR-2 has been shown to play an important role in the induction of T cell anergy and the regulation of peripheral T cell tolerance. In vitro, a prior study has show that T cells deficient in EGR-2 are hyperproliferative to IL-2 and produce elevated levels of the effector cytokine IFN-c. EGR-2 deficient mice have increased levels of CD44 high T cells in peripheral lymphoid organs, and with age, develop autoimmune-like features. Principal Findings: Here we show that despite increased numbers of cells bearing an activated CD44 high CD62L low phenotype, T cells from young healthy EGR-2 deficient mice have normal proliferative and cytokine responses, and the mice themselves mount normal immune responses against minor histocompatibility antigens, and the pathogens Toxoplasma gondii and lymphocytic choriomeningitis virus. Conclusions: Our results indicate that EGR-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as tha

EGR-2 deficient T cells show normal proliferation and cytokine production.

<p>(A) CFSE analysis of purified CD4 T cells after activation with anti-CD3 alone or anti-CD3 and anti-CD28 at the specified conditions. (B) IL-2 production from the cultures described above, measured through ELISA. (C) IFN-γ production of purified CD4 T cells after activation with anti-CD3 and antigen presenting cells, measured by ELISA.</p

EGR-2 deficient mice produce normal levels of INF-g in response to <i>T. gondii</i> infection.

<p>WT (white) or EGR-2 CKO (black) mice were infected with <i>T. gondii</i>. The levels of IFN-γ in the serum were measured on days 7 and 22 through ELISA. Each circle represents a single mouse.</p

EGR-2 deficient mice mount a normal T cell response against LCMV.

<p>WT or EGR-2 CKO mice were infected with 2×10⁵ PFU of LCMV Armstrong. (A) The number of CD8 T cells specific for gp33 or np396 was measured by staining with MHC-class I tetramers, on days 5, 8, and 15. (B) The percentage of CD8 cells that were IFN-γ producers was analyzed by intracellular cytokine staining after restimulation with LCMV pooled peptide. For all graphs, three mice were analyzed for each genotype on each time point.</p

EGR-2 deficient female mice mount a normal response against the Y antigens.

<p>Female WT or EGR-2 deficient mice were injected in the footpad with 20 million total splenocytes from WT male mice. The number of cells in the draining (DLN) and non-draining (NDLN) lymph nodes was calculated and the ratio of DNL/DNLN is shown as fold increase in cellularity. Each condition includes three mice of each genotype.</p

Compilación de Proyectos de Investigacion de 1984-2002

Instituto Politecnico Nacional. UPIICS