Autologous regulation of naive T cell homeostasis within the T cell compartment.
Naive T cells undergo spontaneous slow proliferation on adoptive transfer into syngeneic T cell (T)-deficient hosts. Recent work has shown that such "homeostatic" T cell proliferation is driven by MHC molecules loaded with self-peptides rather than foreign peptides. Because naive T cells in normal T-sufficient hosts remain in interphase despite continuous contact with self-MHC/peptide ligands, T cells apparently inhibit homeostatic proliferation of neighboring T cells. To address this, we have investigated the requirements necessary for "bystander" T cells to inhibit homeostatic proliferation of other T cells. Three key findings are reported. First, homeostatic proliferation of T cells only occurs in specific microenvironments, namely the T cell compartment of the secondary lymphoid tissues. Second, direct entry into T cell compartments is also required for bystander inhibition of homeostatic proliferation. Third, bystander inhibition is mediated largely by naive rather than activated/memory T cells and does not require proliferation or TCR ligation. These findings suggest that homeostasis of naive T cells is unlikely to be regulated through competition for systemic soluble factors or for specific stimulatory self-MHC/peptide ligands. Rather, the data favor mechanisms that involve competition for local non-MHC stimulatory factors or direct cell-to-cell interactions between the T cells themselves within the T cell compartment.
Dummer
W
W
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ernst
B
B
LeRoy
E
E
Lee
D
D
Surh
C
C
D019264:Adoptive Transfer; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation
D000949:Histocompatibility Antigens Class II; D008024:Ligands