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

B. Zaragoza, C. Evaristo, Adrien Kissenpfennig, V. Libri, B. Malissen, B. Rocha, A.A. Freitas, A.R.M. Almeida

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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 naive 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 TCM and TEM 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, TEM-cell expansion was mainly determined by CD4(+) T-cell help and dependent on the expression of IL-2R beta by CD8 cells, on IL-2 produced by CD4(+) T-cells, on IL-15 and to a minor extent on IL-6.
Original languageEnglish
Article numbere17423
JournalPLoS ONE
Issue number3
Publication statusPublished - Mar 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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