Parallels in T lymphocyte development between lpr and normal mice

Abstract

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 CD44 hi and produce large amounts of several cytokines, in contrast to normal murine peripheral T cells. However, the minor CD44 hi subset of normal memory T cells produces similarly high levels of cytokines. The expression of intermediate density surface T cell antigen receptor (TCR)-αβ 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-αβ. 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 p59 fyn, 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.