Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

Lymphopenia-Induced T Cell Proliferation Innate Immune Cell CD45 Regulates

Mathematical modeling reveals the biological program regulating lymphopenia-induced proliferation.

Recognition of peptide-MHC by the TCR induces T lymphocytes to undergo cell division. Although recognition of foreign peptide induces a program of cellular division and differentiation by responding T cells, stimulation by self-peptide MHC complexes in lymphopenic conditions induces a slower burst of divisions that may or may not be accompanied by effector differentiation. Although both respons...

Lymphopenia-Induced Proliferation in Aire-Deficient Mice Helps to Explain Their Autoimmunity and Differences from Human Patients

Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and its mouse model - both caused by mutant AIRE - have greatly advanced the understanding of thymic processes that generate a self-tolerant T-cell repertoire. Much is now known about the molecular mechanisms by which AIRE induces tissue-specific antigen expression in thymic epithelium, and how this leads to nega...

Lymphopenia and autoimmune diseases

More than 30 years ago, the occurrence of spontaneous autoimmune thyroiditis was observed in rodents that were made severely T-cell lymphopenic by neonatal thymectomy or by thymectomy at week five after birth together with concomitant low dose irradiation [1,2]. Following these reports, numerous studies have shown that manipulations that generate functional T-cell lymphopenia result in the deve...

PD-1 Controls Tonic Signaling and Lymphopenia-Induced Proliferation of T Lymphocytes

Recovery of the T lymphocyte compartment within a lymphopenic host by lymphopenia-induced proliferation (LIP) is regulated by inter- and intraclonal competition for limited resources, including homeostatic cytokines and peptide:MHC (pMHC) complexes with which the TCR can interact at least weakly to yield a tonic signal. Importantly, the process of LIP can synergize with other factors that promo...