CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells

作者：Sarin Ritu; Abraham Clara^*

来源：American Journal of Physiology - Gastrointestinal and Liver Physiology, 2012, 303(7): G851-G860.

DOI：10.1152/ajpgi.00520.2011

• T lymphocytes
• costimulation
• adhesion molecules
• cell trafficking

Sarin R, Abraham C. CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells. Am J Physiol Gastrointest Liver Physiol 303: G851-G860, 2012. First published July 19, 2012; doi:10.1152/ajpgi.00520.2011.-Lymphocyte numbers are tightly regulated; with acute lymphopenia, T cell numbers are reestablished through lymphopenia-induced proliferation. In contrast to the co-stimulation requirements of antigen-driven proliferation, a number of costimulatory molecules are not required for lymphopenia-induced proliferation. However, the requirement for major histocompatibility complex (MHC)-T cell receptor (TCR) interactions and the enhanced lymphopenia-induced proliferation in T cells with higher TCR affinity argue for a role for surface molecules that contribute to efficient MHC-TCR interactions, in particular adhesion molecules. CD18 is an integrin that contributes to the activation of peripheral and intestinal T cells through adhesive and costimulatory mechanisms. We found that CD18 is required for optimal polyclonal and monoclonal CD4(+) T cell lymphopenia-induced proliferation in recombination-activating gene 1-deficient (RAG1(-/-)) mice; this requirement persisted over time. Uniquely, the dependency on CD18 in CD4(+) T cells is in the rapid proliferation in RAG-1(-/-) recipients and in the slow homeostatic proliferation in irradiated Balb/c recipients. Consistent with the proposed role for intestinal microbiota in lymphopenia-induced rapid proliferation in RAG(-/-) mice, we observed a significant reduction in rapid proliferation upon treatment of mice with antibiotics; however, the dependency on CD18 for optimal lymphopenia-induced proliferation persisted. Moreover, the dependency for CD18 is maintained over a wide range of numbers of initially transferred T cells, including a low number of initially transferred T cells, when the drive for proliferation is very strong and proliferation is more rapid. Overall, these data argue for an essential and broad role for CD18 in lymphopenia-induced proliferation.

• 出版日期2012-10