The non-classical MAP kinase ERK3 controls T cell activation.

The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response.

Circadian variation of the response of T cells to antigen.

Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored.

Lowering TCR expression on naive CD8+ T cells does not affect memory T-cell differentiation.

The generation of long-lived memory T (Tm) cells is critical for the success of vaccination, but the factors controlling their differentiation are still poorly defined. We examined the hypothesis that the level of T-cell receptor (TCR) engagement contributed to memory CD8(+) T-cell generation. By manipulating TCR expression levels on murine, naive ovalbumin (OVA)-specific CD8(+) T cells, we showed that the expansion of antigen (Ag)-specific CD8(+) T cells is minimally affected by the level of TCR expression.

Memory T-lymphocyte survival does not require T-cell receptor expression.

The factors controlling memory T (Tm)-cell longevity are still poorly defined, and their identification is pivotal to the design of a vaccine conferring long-term protection against infection. Tm cells have the ability to survive in the absence of the T-cell receptor (TCR)-MHC interaction. This does not exclude a possible role for TCR-intrinsic ligand-independent constitutive signaling in Tm-cell homeostasis.

Overexpression of IL-21 promotes massive CD8+ memory T cell accumulation.

The ability of IL-21 to promote in vitro T cell survival led us to investigate its biological activity in vivo. We report that overexpression of IL-21 in transgenic mice drives CD8(+) memory T cell accumulation with a concomitant reduction in naive T cell numbers. These memory T cells are functional, given their ability to rapidly produce IFN-gamma and proliferate following stimulation.

IL-7 receptor expression levels do not identify CD8+ memory T lymphocyte precursors following peptide immunization.

Identification of the mechanisms underlying the survival of effector T cells and their differentiation into memory T lymphocytes are critically important to understanding memory development. Because cytokines regulate proliferation, differentiation, and survival of T lymphocytes, we hypothesized that cytokine signaling dictates the fate of effector T cells. To follow cytokine receptor expression during T cell responses, we transferred murine TCR transgenic T cells into naive recipients followed by immunization with peptide emulsified in adjuvant or pulsed on dendritic cells.