IL-7-dependent homeostatic proliferation in the presence of a large number of T cells in gld mice.
In gld mice, CD4 and 8-double-negative (DN) T cells as well as naive and memory-phenotype T cells accumulate in the peripheral lymphoid organs. Although Fas ligand (L) defect accounts for the progressive accumulation of abnormal DN T cells, the existence of other mechanisms which may be involved in the defective homeostasis in gld mice has been unclear. In this study, we analyze T-cell homeostasis in gld mice using adoptive transfer systems. It was shown that a gld, but not C57BL/6 (B6), environment led to augmented proliferation of B6 T cells transferred without up-regulation of CD69. Thus, the augmented T-cell proliferation seemed to result from mal-homeostatic proliferation even in the presence of a large number of recipient T cells. T cells from lpr mice showed no significant proliferation in the B6 environment, suggesting that the absence of Fas-Fas L interaction was not responsible for the mal-homeostatic proliferation. Although similar levels of IL-7 mRNA were detected in gld and B6 spleens, the intensity of CD127 and the proportion of CD127+ cells in the T cells were significantly lower in gld mice than in B6 mice, suggesting that IL-7 excess in a gld environment is responsible for the abnormal proliferation of transferred T cells. The administration of anti-CD127 antibody inhibited the proliferation of transferred lymphocytes. Thus, IL-7-dependent proliferation seems to be involved in the abnormal proliferation of lymphocytes in gld recipients.
Aranami
Toshimasa
T
Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Iclozan
Cristina
C
Iwabuchi
Kazuya
K
Onoé
Kazunori
K
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division; D053222:Fas Ligand Protein; D005260:Female; D006706:Homeostasis; D015851:Interleukin-7 / Q000032:analysis / Q000502:physiology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020395:Receptors, Interleukin-7 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; D015851:Interleukin-7; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D020395:Receptors, Interleukin-7; D000099192:CD69 Antigens; C505658:Fasl protein, mouse