Parallels in T lymphocyte development between lpr and normal mice.
The unusual phenotype and function of lpr T cell subsets has considerably aided the determination of various stages in normal T lymphocyte development through the identification of parallel populations. This has included the description of memory T cells that express high levels of CD44. Lpr mature (CD4+ and CD8+) T cells are all CD44hi and produce large amounts of several cytokines, in contrast to normal murine peripheral T cells. However, the minor CD44hi subset of normal memory T cells produces similarly high levels of cytokines. The expression of intermediate density surface T cell antigen receptor (TCR)-alpha beta by lpr CD4-, CD8- (CD4-8-) cells guided the identification of a minor subset of Heat Stable Antigen--normal CD4-8- thymocytes that also expresses TCR-alpha beta. The unresponsiveness of lpr CD4-8- T cells correlates closely with their absence of CD2 expression. This is paralleled in normal mice by CD2- and CD2+ subsets of thymocytes and gut lymphocytes in which the proliferative capacity also segregates with CD2 expression. Finally, lpr CD4-8- T cells bear many similarities to anergic T cells, including high expression of p59fyn, lack of IL-2 production, and recovery of function following induction of cell cycling in the presence of IL-2. The developmental block in lpr CD4-8- T cells has therefore provided considerable insight into normal T cell development and function.
Budd
R C
RC
Department of Medicine, University of Vermont College of Medicine, Burlington 05405.
Van Houten
N
N
Clements
J
J
Mixter
P F
PF
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D015703:Antigens, CD; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta