Peripheral human CD8+CD28+T lymphocytes give rise to CD28–progeny, but IL-4 prevents loss of CD28 expression

Labalette, Myriam; Leteurtre, Emmanuelle; Thumerelle, C.; Grutzmacher, C.; Tourvieille, Béatrice; Dessaint, Jean-Paul

doi:10.1093/intimm/11.8.1327

Cited by 44 publications

(49 citation statements)

References 29 publications

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“…The CD28 molecule is lost by normal lymphocytes after repeated stimulation with IL-2 in long-term culture (Labalette et al, 1999). Based on the fact that T lymphocytes from B-CLL patients have a phenotype of activated cells, that is, Dianzani et al, 1994;Van den Hove et al, 1998;Scrivener et al, 2001), it can be suggested that the loss of CD28 molecule on T lymphocytes before culture is related to a prolonged in vivo activation of these cells.…”

Section: Discussionmentioning

confidence: 99%

Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia

et al. 2004

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In the present study, we have examined the kinetics and magnitude of expression of the CD28 and CD152 molecules on unstimulated and anti-CD3 þ rIL-2-stimulated peripheral blood CD4 þ and CD8 þ T cells in patients with chronic lymphocytic leukaemia (B-CLL) and controls. The mean percentages of both CD3 þ /CD4 þ /CD28 þ and CD3 þ /CD8 þ /CD28 þ cells were significantly lower in B-CLL than in controls before culture, decreased rapidly, reaching their lowest levels between 24 and 48 h, and returned to basal levels after 72 h of culture. In controls, the lowest proportions of CD3 þ /CD4 þ /CD28 þ and CD3 þ /CD8 þ / CD28 þ cells were found after 24 h and returned to prestimulation levels after 48 h of stimulation. We observed significantly higher proportions of unstimulated CD3 þ /CD4 þ /CD152 þ and CD3 þ /CD8 þ /CD152 þ cells in B-CLL patients than in controls. The highest percentages of CD3 þ /CD4 þ /CD152 þ and CD3 þ /CD8 þ /CD152 þ cells were observed in controls after 72 h, and in B-CLL patients after 24 h, and remained statistically higher after 48, 72 and 96 h of stimulation. CD152 molecule expression returned to prestimulation levels after 96 h of culture in controls, and after 120 h in B-CLL patients. The abnormal kinetics and levels of CD28 and CD152 expression on T cells in B-CLL may lead to a state of hyporesponsiveness or anergy and could be one of the mechanisms of immune deficiency in this disease.

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Section: Discussionmentioning

confidence: 99%

Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia

et al. 2004

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“…Allogeneic, phytohaemagglutinin or anti-CD3 stimulation of CD8+ CD28+ T cells gives rise to a CD8+ CD28¡ T cell population [71]; this was accelerated by the presence of type I IFN [99]. Loss of CD28 has also been demonstrated for cord blood cells cultured in IL-12 and IL-15 [100], naïve cells maintained in IL-15 (reversed by IL-21) [101] and CD8+ CD28+ cells propagated using soluble anti-CD3 antibody and IL-2 (reversed by IL-4) [102]. Taken together these studies provide a strong indication that CD8+ CD45RA+ CD28¡ T cells develop in conditions of antigen absence in a particular cytokine environment, although it is unclear why this occurs to a greater extent during HCMV infection compared to other chronic viral infections.…”

Section: What Is the Lineage Relationship Of Cd45ra+ Cd28¡ (Revertantmentioning

confidence: 95%

Dynamics of T cell memory in human cytomegalovirus infection

Waller

Day

Sissons

et al. 2008

Med Microbiol Immunol

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Primary human cytomegalovirus (HCMV) infection of an immunocompetent individual leads to the generation of a robust CD4+ and CD8+ T cell response which subsequently controls viral replication. HCMV is never cleared from the host and enters into latency with periodic reactivation and viral replication, which is controlled by reactivation of the memory T cells. In this article, we discuss the magnitude, phenotype and clonality of the T cell response following primary HCMV infection, the selection of responding T cells into the long-term memory pool and maintenance of this memory T cell population in the face of a latent/persistent infection. The article also considers the eVect that this long-term surveillance of HCMV has on the T cell memory phenotype, their diVerentiation, function and the associated concepts of T cell memory inXation and immunosenescence.

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“…The lack of a difference in some experiments appeared to be related to the time point analyzed, with day 7 showing a difference in all experiments, day 8 in most, and day 9 in none, even in the same donor. In most donors, effector T cells maintained the expression of CD28 for the 7-8 days of culture, but by 9 days higher numbers of CD28 Ϫ T cells were observed in some donors, perhaps due to the accumulation of cytokines that are known to modulate the expression of CD28 (30)(31)(32). These data suggest that 4-1BBL can be more effective than B7.1 in driving human memory T cells into mature CD27 Ϫ effector cells, at least under some conditions.…”

Section: -1bbl and B71 Costimulation And The Efficacy Of Effector Tmentioning

confidence: 99%

Costimulatory ligand 4-1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses

Bukczynski

Wen

Ellefsen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

100

106

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Effective adjuvants capable of inducing strong cytotoxic T cell responses in humans are lacking. In this study, we tested 4-1BBL as an adjuvant for activation of human memory antiviral CD8 T cell responses ex vivo. A recombinant replication-defective 4-1BBL adenovirus was used to convert autologous monocytes into efficient antigen-presenting cells after overnight incubation, bypassing the need to generate dendritic cells. Together with viral peptides, 4-1BBL led to robust memory responses of human EpsteinBarr virus-and influenza virus-specific cytotoxic T cells, with expansion of peptide-specific CD8 effector cells; up-regulation of Bcl-x L, granzyme A, and perforin; enhanced cytotoxic activity; and increased cytokine production. The response was significant even at a 100-fold lower peptide dose, compared with responses obtained with control adenovirus. Adenovirus-delivered B7.1 also expanded and activated virus-specific CD8 T cells, but 4-1BBL was more effective in driving the T cells toward a more fully differentiated CD27 ؊ effector state. Thus, 4-1BBL is a promising adjuvant for human memory CD8 T cells and will likely be most effective in the boost phase of a prime-boost strategy.E fficient activation of the cellular arm of the immune system requires a specific T cell antigen receptor signal delivered upon recognition of peptide͞MHC together with costimulatory signals. It has now been well established that dendritic cells are potent antigen-presenting cells (APC) for initiation of immune responses (1). Upon maturation, these cells up-regulate costimulatory molecules required for T cell activation. As a result, there is now considerable interest in the use of dendritic cells loaded with antigens as adjuvants for therapeutic vaccines (2, 3). A limitation of this approach is the need to derive the syngeneic dendritic cells in culture, a process that takes 7 days. In this report we describe the conversion of monocytes into efficient APC for activation of T cell memory responses by overnight incubation with recombinant adenoviruses expressing costimulatory molecules.Although the best characterized costimulatory molecule is CD28, recently other costimulatory molecules have been characterized (4-6). The emerging picture is that CD28 is important for the initial activation of an immune response and that other costimulatory ligand-receptor pairs act later to help sustain and diversify the response (4-6).4-1BB is an inducible costimulatory member of the tumor necrosis factor receptor family expressed on activated CD4 and CD8 T cells. Its ligand, 4-1BBL, is expressed on activated APC (6, 7). 4-1BB can enhance both the proliferation and the survival of murine CD4 and CD8 T cells (8)(9)(10)(11)(12)(13)(14). Recent evidence in mouse models suggests that 4-1BB͞4-1BBL interaction plays an important role in the memory CD8 T cell response to viruses (15-18).In humans, several studies have looked at the role of 4-1BBL or anti-4-1BB in polyclonal activation of T cells, but the specific role of 4-1BBL in activation of antigen-s...

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Peripheral human CD8+CD28+T lymphocytes give rise to CD28–progeny, but IL-4 prevents loss of CD28 expression

Cited by 44 publications

References 29 publications

Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia

Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia

Dynamics of T cell memory in human cytomegalovirus infection

Costimulatory ligand 4-1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses

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