Memory T cells have gene expression patterns intermediate between naive and effector - PubMed (original) (raw)

Memory T cells have gene expression patterns intermediate between naive and effector

Susan Holmes et al. Proc Natl Acad Sci U S A. 2005.

Abstract

The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM cells (parallel differentiation) remains unresolved. We isolated NAI, EFFE, and MEM CD8(+) T cell subsets from human peripheral blood and analyzed their gene expression by using microarrays. We identified 156 genes that strongly differentiate NAI, EFFE, and MEM CD8(+) T cells; these genes provide previously unrecognized markers to help identify each cell type. Using several statistical approaches to analyze and group the data (standard heat-map and hierarchical clustering, a unique circular representation, multivariate analyses based on principal components, and a clustering method based on phylogenetic parsimony analysis), we assessed the lineage relationships between these subsets and showed that MEM cells have gene expression patterns intermediate between NAI and EFFE T cells. Our analysis suggests a common differentiation pathway to an intermediate state followed by a split into EFFE or MEM cells, hence supporting the parallel differentiation model. As such, conditions under which NAI T cells are activated may determine the magnitude of both EFFE and MEM cells, which arise subsequently. A better understanding of these conditions may be very useful in the design of future vaccine strategies to maximize MEM cell generation.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Boxplots of sample genes demonstrating expression ranges in each cell type: selectin-L (A), IL-7R (B), and granzyme. B (C).

Fig. 2.

Fig. 2.

Graphical representations of patterns of differential expression for the set of 156 significant genes: angular representation of genes (A), standardized scatter plot (B), and histogram of angles (C).

Fig. 3.

Fig. 3.

First principal plane from the principal components analysis of the matrix of significant genes in all 30 samples.

Fig. 4.

Fig. 4.

Tree representations of arrays: hierarchical clustering of arrays (A) and parsimony tree (B).

Similar articles

Cited by

References

    1. Opferman, J. T., Ober, B. T. & Ashton-Rickardt, P. G. (1999) Science 283, 1745–1748. - PubMed
    1. Kaech, S., Tan, J., Wherry, E., Konieczny, B., Surh, C. & Ahmed, R. (2003) Nat. Immunol. 4, 1191–1198. - PubMed
    1. Manjunath, N., Shankar, P., Wan, J., Weninger, W., Crowley, M. A., Hieshima, K., Springer, T. A., Fan, X., Shen, H., Lieberman, J. & von Andrian, U. H. (2001) J. Clin. Invest. 108, 871–878. - PMC - PubMed
    1. Kaech, S., Hemby, S., Kersh, E. & Ahmed, R. (2002) Cell 111, 837–851. - PubMed
    1. Manjunath, N., Shankar, P., Stockton, B., Dubey, P. D., Lieberman, J. & von Andrian, U. H. (1999) Proc. Natl. Acad. Sci. USA 96, 13932–13937. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources