Molecular signature of mice T lymphocytes following tolerance induction by allogeneic BMT and CD40-CD40L costimulation blockade.

Tolerance induction by mixed chimerism and costimulation blockade is a promising approach to avoid immunosuppression, but the molecular basis of tolerant T lymphocytes remains elusive. We investigated the genome-wide gene expression profile of murine T lymphocytes after tolerance induction by allogeneic bone marrow transplantation (BMT) and costimulatory blockade using the anti-CD40L antibody MR1. Molecular functions, biological processes, cellular locations, and coregulation of identified genes were determined. A total of 113 unique genes exhibited a significant differential expression between the lymphocytes of MR1-treated Tolerance (TOL) and untreated recipients Control (CTRL). The majority of genes upregulated in the TOL group are involved in several signal transduction cascades such as members of the MAPKKK cascade (IL6, Tob2, Stk39, and Dusp24). Other genes involved in lymphocyte differentiation and highly expressed in the TOL group are lymphotactin, the estrogen receptors (ERs) and the suppressor of cytokine signaling 7. Common transcription factors such as ER 1 alpha, GATA-binding protein 1, insulin promoter factor 1, and paired-related homeobox 2 could be identified in the promoter regions of upregulated genes in the TOL group. These data suggest that T lymphoctes of tolerant mice exhibit a distinct molecular expression profile, which needs to be evaluated in other experimental tolerance models to determine whether it is a universal signature of tolerance.