Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice.
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A null mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A-deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte responses.
Stanford
W L
WL
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7455, USA.
Haque
S
S
Alexander
R
R
Liu
X
X
Latour
A M
AM
Snodgrass
H R
HR
Koller
B H
BH
Flood
P M
PM
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003432:Cross-Linking Reagents; D015536:Down-Regulation; D005434:Flow Cytometry; D018390:Gene Targeting; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D000950:Antigens, Ly; D003432:Cross-Linking Reagents; D007519:Isoantigens; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D003208:Concanavalin A; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin