Dataset Information

Identification of two major types of age-associated CD8 clonal expansions with highly divergent properties.

ABSTRACT: CD8 memory T cells are tightly regulated in young, healthy individuals but are often perturbed in aged animals by the appearance of large CD8 T cell clones. These clones are associated with impaired immunity in the aged. The molecular basis of this phenomenon remains unclear. Here, it is shown that the issue is confused by the fact that the clones are heterogeneous. Some clones bear high, and others, low levels of integrin alpha(4) (itgalpha4). These subtypes differ by multiple criteria. They appear in mice of different ages, concentrate in different tissues, and have different stabilities in vivo and responses to stimulation in vitro. itgalpha4(high), but not itgalpha4(low), CD8 clonal expansions have several characteristics consistent with a chronically stimulated phenotype. These properties include lowered levels of CD8, decreased expression of some cytokine receptors, and elevated expression of various inhibitory receptors, including the programmed death-1 (PD1) receptor and the killer cell lectin-like receptor G1 (KLRG1). The characteristics of itgalpha4(high) clonal expansions suggest that they may arise from age-dependent alterations in antigen expression and tolerance. These data redefine CD8 clonal expansions into at least two distinct entities and indicate that there are multiple mechanisms that drive age-related alterations of CD8 T cell homeostasis.

SUBMITTER: Clambey ET

PROVIDER: S-EPMC2525558 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Many aged individuals develop monoclonal expansions of CD8 T cells. These expansions are derived from a CD8 memory T cell that outcompetes neighboring CD8 T cells. The molecular alterations within clonal expansions that confer this competitive advantage relative to other CD8 T cells remains unknown. These microarray experiments were designed to identify genes differentially expressed in age-associated expansions of CD8 memory T cells relative to polyclonal CD8 memory T cells found in the same aged mice. Subsequent analysis of these data identified two major types of clonal expansions, distinguished by expression level of integrin a4 mRNA and protein. Based on this classification, Expansion_rep1 belongs to the integrin a4 high subtype of clonal expansions. In contrast, reps 2, 4, and 5 belong to the integrin a4 low subtype of clonal expansions. Given the divergent biological properties of these two subtypes of clonal expansions, we have focused genes differentially expressed between Expansion_rep 2, 4, and 5 and their paired PolyclonalAged samples. Experiment Overall Design: A total of 8 samples were analyzed for gene expression using the Affymetrix mouse genome 430 2.0 microarray platform. The experimental samples of interest were age-associated clonal expansions of CD8 memory T cells. We purified four clonal expansions from four independent, aged mice (indicated as "Expansion" rep1 2, 3, 4). For each clonal expansion of CD8 memory T cells that was purified, there was a paired control in which polyclonal CD8 memory T cells were harvested from the same aged mouse (denoted as "PolyclonalAged" rep1, 2, 3, 4). These paired samples allow one to consider gene expression changes from mice which have undergone the same age-associated changes in biology. The predominant comparison this study focused on was changes in gene expression between age-associated clonal expansions of CD8 memory T cells and their paired, polyclonal CD8 memory T cells. A total of 4 of these pairs were collected.

Dataset Information

Identification of two major types of age-associated CD8 clonal expansions with highly divergent properties.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure