Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8.sup.+ T.sub.CM and T.sub.EM Cell Pools

• Published in: PloS one 2011-03, Vol.6 (3), p.e17423
• Main Authors: Zaragoza, Bruno, Evaristo, César, Kissenpfennig, Adrien, Libri, Valentina, Malissen, Bernard, Rocha, Benedita, Freitas, António A, Almeida, Afonso R. M
• Format: Article
• Language: English
• Subjects: B cells; Interferon; Interleukins; T cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017423

We here describe novel aspects of CD8.sup.+ and CD4.sup.+ T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8.sup.+ T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8.sup.+ T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4.sup.+ 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.sup.+ 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.sup.+ CD62L.sup.high) T.sub.CM and (CD44.sup.+ CD62L.sup.low) T.sub.EM CD8.sup.+ T cells, we found that the accumulation of T.sub.CM and T.sub.EM subsets is differentially regulated. T.sub.CM -cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4.sup.+ T-cell help. In contrast, T.sub.EM -cell expansion was mainly determined by CD4.sup.+ T-cell help and dependent on the expression of IL-2R[beta] by CD8 cells, on IL-2 produced by CD4.sup.+ T-cells, on IL-15 and to a minor extent on IL-6.