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Public Library of Science, PLoS ONE, 3(6), p. e17423, 2011

DOI: 10.1371/journal.pone.0017423

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Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8 T(CM) and T(EM) Cell Pools.

Journal article published in 2011 by Bruno Zaragoza, César Evaristo, Adrien Kissenpfennig, Valentina Libri ORCID, Bernard Malissen ORCID, Benedita Rocha, António A. Freitas, Afonso R. M. Almeida
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

We here describe novel aspects of CD8(+) and CD4(+) T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8(+) T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8(+) T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4(+) T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4(+) T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44(+)CD62L(high)) T(CM) and (CD44(+)CD62L(low)) T(EM) CD8(+) T cells, we found that the accumulation of T(CM) and T(EM) subsets is differentially regulated. T(CM)-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4(+) T-cell help. In contrast, T(EM)-cell expansion was mainly determined by CD4(+) T-cell help and dependent on the expression of IL-2Rβ by CD8 cells, on IL-2 produced by CD4(+) T-cells, on IL-15 and to a minor extent on IL-6.