CD2(-)CD4(-)CD8(-) LYMPH-NODE T-LYMPHOCYTES IN MRL LPR LPR MICE ARE DERIVED FROM A CD2(+)CD4(+)CD8(+) THYMIC PRECURSOR
- Author(s)
- LANDOLFI, MMT; VANHOUTEN, N; RUSSELL, JQ; Scollay, R; PARNES, JR; Budd, RC;
- Details
- Publication Year 1993-07-15,Volume 151,Issue #2,Page 1086-1096
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- MRL lpr/lpr (lymphoproliferative, lpr) mice demonstrate an age-dependent lymphoproliferation and development of autoimmunity. Characteristic of the lymphoproliferation in these mice is the accumulation of large numbers of CD4-CD8- (CD4-8-), CD3+ T lymphocytes in their lymph nodes. The development of the CD4-8- cells, which also aberrantly express B220 and CD44 (Pgp-1) but are CD2-, has been shown to be thymus dependent. An unusual feature of lpr CD4-8- T lymphocytes is that although they appear unresponsive to stimulation, as defined by proliferation and IL-2 production, they have undergone thymic negative selection. As thymic deletion normally occurs at the CD4+CD8+ (CD4+8+) stage, this raises the dilemma that lpr CD4-8- T lymphocytes have either previously been CD4+8+, or they are able to undergo thymic selection as CD4-8- cells. We have addressed this question by examining the methylation status of the CD8 gene in MRL lpr CD4-8- lymph node cells. Demethylation of the CD8 gene has been shown to be an indicator of previous CD8 expression. We find that the CD8 gene in lpr CD4-8- lymph node cells, as well as in the abnormal B220+CD4-8- lpr thymocytes, is demethylated, suggesting that these cells have previously expressed CD8. In addition, we find that the lpr CD4+8+ thymocyte population contains an increased percentage of atypical B220+, CD44+ cells that are virtually all CD2+. Taken together, these data are consistent with the lpr CD2-CD4-8- population of LNC having arisen from a CD2+CD4+8+ thymic stage of differentiation.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- CELL-RECEPTOR; LPR/LPR MICE; ALPHA-BETA; ANTIGEN; EXPRESSION; THYMOCYTES; GENE; ACTIVATION; SELECTION; DELETION
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Creation Date: 1993-07-15 12:00:00