Reevaluation of the origin of CD44high "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells

Abstract

CD44highCD8 T cells in naive mice, which increase with age, and are often referred to as memory CD8 T cells. However, since thymus‐independent CD8 T cells have also been shown to be CD44high, the origin of the CD44highCD8 T cells in naive mice remains unclear. In this study, we compared the characteristics of memory CD8 T cells and thymus‐independent CD8 T cells in TCR transgenic mice to clarify the origin of the CD44highCD8 T cells in naive normal mice. The memory and thymus‐independent CD8 T cells showed differences in surface molecules, spontaneous cell death, cytokine production, and response to IL‐2R binding of cytokines. Importantly, the "memory phenotype" CD8 T cells in naive normal mice showed similar characteristics to the thymus‐independent CD8 T cells, but differed greatly from "true" memory CD8 T cells in the TCR transgenic mice. Therefore, we conclude that a significant part of the CD44high memory phenotype CD8 Tcells in naive normal mice represents thymus‐independent CD8 T cells, which may participate in age‐related changes in immune responses.

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

“…In agreement with a previous study, 8 we found that the CD8 lo cells proliferated poorly to antigen stimulation in the absence of IL-2 ( Figure 2A, upper panel). The CD8 int cells also showed a similar proliferative defect.…”

“…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.…”

“…11,12 CD8 ϩ T cells that develop via an extrathymic pathway and possessing similar functional characteristics are also found in normal (non-TCR transgenic) mice. 8 More importantly, cells of this phenotype in normal mice have also been shown to be important in responses toward viral and bacterial infections, suggesting that they may have an important role in the immune response. 13,14 We have recently showed that CD8 ϩ CD44 hi T cells from normal mice possess characteristics of both T cells and NK cells.…”

Differential In Vivo Persistence of Two Subsets of Memory Phenotype CD8 T Cells Defined by CD44 and CD122 Expression Levels

“…However, these cells also proliferate weakly in response to anti-CD3 plus anti-CD28 stimulation (data not shown). In this respect they are similar to memory phenotype CD8 T cells, which are generated following homeostatic proliferation in other TCR-transgenic systems (6) and to thymus-independent T cells (33). This last point highlights the fact that CD44 high CD122 ϩ CD8 T cells in F5 but also in wild-type mice, where they are classically identified as memory cells, could be heterogeneous not only in their antigenic specificity but also in their generation requirements.…”

CD40 Ligation In Vivo Induces Bystander Proliferation of Memory Phenotype CD8 T Cells

“…However, during homeostatic or lymphopenia-induced proliferation, naive CD8 T cells can also acquire a memory phenotype, as shown by up-regulation of CD44 and KLRG1, and by their ability to secrete cytokines (47)(48)(49)(50). CD44 high memory phenotype CD8 T cells in normal naive mice have also been shown to exhibit characteristics similar to thymus-independent CD8 T cells (51). Thus, many memory phenotype CD8 T cells may not be true Agexperienced memory cells.…”