Details

Autor(en) / Beteiligte

• Parsons, Michael J
• Jones, Russell G
• Tsao, Ming-Sound
• Odermatt, Bernard
• Ohashi, Pamela S
• Woodgett, James R

Titel

Expression of Active Protein Kinase B in T Cells Perturbs Both T and B Cell Homeostasis and Promotes Inflammation

Ist Teil von

• The Journal of immunology (1950), 2001-07, Vol.167 (1), p.42-48

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• The molecular mechanisms that contribute to autoimmunity remain poorly defined. While inflammation is considered to be one of the major checkpoints in autoimmune disease progression, very little is known about the initiating events that trigger inflammation. We have studied transgenic mice expressing the prosurvival molecule protein kinase B/Akt under control of a T cell-specific CD2 promoter. In this study, we demonstrate that aged mice develop lymphadenopathy and splenomegaly that result from an accumulation of CD4, CD8, and unexpectedly B cells. An increased proportion of T cells express activation markers, while T cell proliferative responses remain normal. B cells are hyperproliferative in response to anti-IgM F(ab')(2) and anti-CD40, and increased IgA and IgG2a were found in the sera. In addition, a profound multiorgan lymphocytic infiltration is observed, and T cells from these mice display a defect in Fas-mediated apoptosis, which may be the mechanism underlying this phenotype. Therefore, T cell expression of active protein kinase B can alter T cell homeostasis, indirectly influence B cell homeostasis, and promote inflammation in vivo.