Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice.
To investigate the role of interleukin 7 (IL-7) in the development of the lymphoid system, we have generated two lines of transgenic mice carrying an IL-7 cDNA fused to an immunoglobulin heavy chain promoter and enhancer. This transgene is expressed in the bone marrow, lymph nodes, spleen, thymus, and skin provoking a perturbation of T cell development characterized by a marked reduction of CD4+ CD8+ (double-positive) thymocytes. Quite unexpectedly, however, both lines also develop a progressive cutaneous disorder involving a dermal lymphoid infiltrate that results in progressive alopecia, hyperkeratosis, and exfoliation. Although the infiltrate is primarily composed of T lineage cells, its development is not impeded in the athymic nu/nu background. Furthermore, the phenotype can be transmitted horizontally by transplanting lymphoid tissues or skin to syngeneic wild-type mice. Thus, the phenotype is conveyed by skin-homing, mobile cells (presumably the infiltrating lymphocytes) in a cell-autonomous fashion. In addition to the skin phenotype, this transgene also provokes the development of a lymphoproliferative disorder that induces B and T cell lymphomas within the first 4 mo of life. These findings suggest potential physiologic actions of IL-7 in T cell development and in cutaneous immunity. They also demonstrate that IL-7 can act as an oncogene in the living organism.
Rich
B E
BE
Howard Hughes Medical Institute, Boston, Massachusetts.
Campos-Torres
J
J
Tepper
R I
RI
Moreadith
R W
RW
Leder
P
P
D000505:Alopecia / Q000209:etiology; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018956:CD5 Antigens; D002455:Cell Division; D015870:Gene Expression; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D015851:Interleukin-7 / Q000502:physiology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology; D008223:Lymphoma / Q000209:etiology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology; D016038:Skin Transplantation / Q000473:pathology; D018800:Thy-1 Antigens
D015703:Antigens, CD; D000954:Antigens, Surface; D017252:CD3 Complex; D018956:CD5 Antigens; D015851:Interleukin-7; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018800:Thy-1 Antigens