title: CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells.
abstract: Lymphocyte numbers are tightly regulated; with acute lymphopenia, T cell numbers are reestablished through lymphopenia-induced proliferation. In contrast to the costimulation 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 (RAG-1-/-) 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.
authors: Department of Medicine, Yale University, 333 Cedar St., 1080 LMP, New Haven, CT 06520, USA.
authors: Ritu
authors: R
authors: Sarin
authors: Clara
authors: C
authors: Abraham
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D018821:CD18 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007109:Immunity / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D061025:Costimulatory and Inhibitory T-Cell Receptors; D018398:Homeodomain Proteins; C064658:RAG-1 protein