An unusual lineage of alpha/beta T cells that contains autoreactive cells.

Abstract

In male mice that express a transgenic alpha/beta T cell receptor (TCR) specific for a male-specific peptide presented by class I Db major histocompatibility complex (MHC) molecules, we describe an unusual lineage of alpha/beta T cells that are thymus dependent but do not require selection by Db MHC molecules on thymic epithelium in the absence of the specific peptide (positive selection). These cells express the transgenic alpha/beta TCR and have the CD4-8- or CD4-8low phenotype. Cells with the latter phenotype are only detected when hemopoietic cells express both the male-specific peptide as well as Db MHC molecules. In fact, these cells are autoreactive, as they expand relatively slowly after transfer into male nude mice. Also in male but not female alpha/beta TCR transgenic mice, the CD8+ cells with the transgenic TCR bear the Pgp1 marker characteristic of mature T cells activated by antigen. CD4-8- as well as CD4-8low cells do not respond significantly when cultured with male stimulator cells but proliferate vigorously when stimulated by TCR antibodies. By this latter criterion, cells in the periphery of male alpha/beta TCR transgenic mice differ from mature male-specific T cells from female alpha/beta TCR transgenic, which become intrinsically anergic when transferred into male nude mice and cannot be stimulated significantly by TCR antibodies. Thus, intrathymic deletion does not eliminate all autoreactive T cells and it is possible that cells with an apparently "benign" autoreactivity may be involved in certain forms of autoimmunity.

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

“…However, they differ from conventional memory T cells in that they are more refractory to activation by antigen compared with naive T cells. 7,8 von Boehmer et al 5 have shown that the development of CD8 lo cells is thymus dependent, since the cells are not found in male H-2 b H-Y nude mice. By contrast, Yamada et al 6 found that CD8 lo cells developed normally in thymectomized male but not female H-2 b mice.…”

“…3 Interestingly, there is a population of CD8 ϩ T cells, which express a low level of CD8 (referred to as CD8 lo ), that are resistant to deletion in male mice. 4,5 The CD8 lo cells are selfreactive, as they expand after transfer into male but not female H-2 b nude mice. 5 These cells express high levels of CD44 5 and interleukin-2 receptor ␤ (IL-2R␤; CD122) 6 that are characteristic of memory T cells.…”

“…4,5 The CD8 lo cells are selfreactive, as they expand after transfer into male but not female H-2 b nude mice. 5 These cells express high levels of CD44 5 and interleukin-2 receptor ␤ (IL-2R␤; CD122) 6 that are characteristic of memory T cells. However, they differ from conventional memory T cells in that they are more refractory to activation by antigen compared with naive T cells.…”

Development of T cells expressing an altered TCR complex

“…The presence of an § / g TCR + CD4 -CD8 -T cell population is a unique feature of TCR transgenic mice [21][22][23]. While different mechanisms may explain how such cells arise in these animals [21,23], it is likely that the current study could simply represent another example of TCR transgenic animals containing these CD4 -CD8 -T cells.…”

Central tolerance: Essential for preventing autoimmune disease?

“…Initially, this finding could have been misinterpreted because the premature expression of the transgenic TCR leads to lineage diversion of some double negative (DN) cells into the DNgd lineage [26][27][28]. This was taken as evidence that in these mice there was only a developmental arrest at the DN stage rather than deletion of DP thymocytes [29].…”