CD4+CD8- T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse.
Mice hemizygous for the X-linked mutation, scurfy (sf), exhibit a fatal lymphoreticular disease that is mediated by T lymphocytes. To evaluate the respective roles of CD4 or CD8 single positive T cells in scurfy disease, neonates were treated with mAbs directed against the CD4 or CD8 molecules. Whereas mice treated with an anti-CD8 Ab developed lesions and succumbed to disease at the same time (17 days) as their untreated scurfy littermates, mice treated with an anti-CD4 Ab lived up to 11 wk before developing scurfy disease. To insure a more complete elimination of the T cell subsets, the scurfy mutation was bred onto beta 2-microglobulin (beta 2m)-deficient (CD8-less) and CD4-deficient transgenic mouse lines. Whereas there was little moderation of disease in beta 2m-deficient scurfy mice, CD4-deficient scurfy mice had markedly decreased scurfy lesions and a prolonged life span, similar to that of anti-CD4-treated sf/Y mice. Additionally, scurfy disease was transplanted into H-2-compatible nude mice through the adoptive transfer of CD4+CD8- T cells, but not CD4-CD8+ T cells. Flow-cytometric analysis revealed that sf/Y mice have an increased percentage of activated CD4+ T cells in their lymph nodes. In addition, there is an increase in the in vitro production of cytokines in the cultured splenocytes of CD8-less, but not CD4-less, scurfy mice. These data suggest that CD4+ T cells are critical mediators of disease in the scurfy mouse.
Blair
P J
PJ
Biology Division, Oak Ridge National Laboratory, TN 37831-8077.
Bultman
S J
SJ
Haas
J C
JC
Rouse
B T
BT
Wilkinson
J E
JE
Godfrey
V L
VL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007111:Immunity, Cellular; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D008819:Mice, Nude; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency
D016207:Cytokines; D001613:beta 2-Microglobulin