Homeostatic proliferation and survival of naïve and memory T cells

Abstract

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naïve T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naïve cells, typical "central" memory T cells rely on a combination of IL-7 and IL-15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T-cell subsets are less quiescent and include naturally occurring activated memory-phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T-cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

“…This suggests that this intestine-specific population is different from the other IgA + memory B-cell populations of intestines or other lymphoid tissues. One possibility is that this population might represent the intestine-specific ef- fector memory B cells, whereas the others are more like central memory B cells, analogues to the division of effector and central memory T cells (25). Although further studies are required to determine whether this is the case, it is clear that CCR10 is required in the maintenance of IgA + memory B cells specifically in the intestines, which correlates well with the specific CCR10 expression by the intestinal IgA + memory-like B cells.…”

Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications

“…These cytokines are IL-7, IL-15 and IL-21. Interleukin-7 is involved in CD4 + T cell expansion, whereas IL-15 and IL-21 are rather implicated in CD8 + T cell expansion (Boyman et al, 2009). Interleukin-7 activity may be neutralized by a soluble form of IL-7 receptor (sIL-7R) (Rose et al, 2009).…”

“…This process, also called lymphopenia-induced proliferation, has been extensively studied in mice (for a review, Boyman et al, 2009). In murine models, this homeostatic proliferation expansion requires homeostatic cytokines (e.g., IL-7) and sometimes cognate antigen-driven interactions ( Fig.1; Boyman et al, 2009).…”

“…This process, also called lymphopenia-induced proliferation, has been extensively studied in mice (for a review, Boyman et al, 2009). In murine models, this homeostatic proliferation expansion requires homeostatic cytokines (e.g., IL-7) and sometimes cognate antigen-driven interactions ( Fig.1; Boyman et al, 2009). Several features with clinical consequences for lymphopenic patients are associated with homeostatic proliferation expansion: a limited TCR repertoire diversity, a shift from naive to memory/activated phenotype in the proliferating cells, a competition for limiting levels of homeostatic cytokines (increasing TCR repertoire skewing, hence decreasing the capacity of the host to respond to antigen challenge), a more delayed T cell recovery (Williams et al, 2007), a possibility to lose transplantation tolerance (Wu et al, 2004) or to favor autoimmunity by expanding autoreactive memory T cells (Monti et al, 2008).…”

“…Interleukin-7 can be considered as a true regulator of the naive T cell pool size, driving homeostatic proliferation of CD4 + CD31 + RTE with sustained CD31 expression (Azevedo et al, 2009). Memory CD4 + T cells express high levels of CD127 (Boyman et al, 2009), then compete with RTE for IL-7. Dependency on IL-15 or IL-21 for homeostatic proliferation expansion is less marked for CD4 + T cells than CD8 + T cells.…”