Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells

Abstract

Virus-specific CD8(+) T-cell responses play a pivotal role in limiting viral replication. Alterations in these responses, such as decreased cytolytic function, inappropriate maturation, and limited proliferative ability could reduce their ability to control viral replication. Here, we report on the capacity of HIV-specific CD8(+) T cells to secrete cytokines and proliferate in response to HIV antigen stimulation. We find that a large proportion of HIV-specific CD8(+) T cells that produce cytokines in response to cognate antigen are unable to divide and die during a 48-hour in vitro culture. This lack of proliferative ability of HIV-specific CD8(+) T cells is defined by surface expression of CD57 but not by absence of CD28 or CCR7. This inability to proliferate in response to antigen cannot be overcome by exogenous interleukin-2 (IL-2) or IL-15. Furthermore, CD57 expression on CD8(+) T cells, CD4(+) T cells, and NK cells is a general marker of proliferative inability, a history of more cell divisions, and short telomeres. We suggest, therefore, that the increase in CD57(+) HIV-specific CD8(+) T cells results from chronic antigen stimulation that is a hallmark of HIV infection. Thus, our studies define a phenotype associated with replicative senescence in HIV-specific CD8(+) T cells, which may have broad implications to other conditions associated with chronic antigenic stimulation.

Subject classification obtained by cluster analysis and principal component analysis applied to flow cytometric data

“…generated by these techniques is difficult to analyze and thus computer assistance and mathematical algorithms are absolutely necessary for data interpretation. This problem is enhanced in polychromatic flow cytometry because the analysis is performed on single cells; as a consequence, hundreds of subsets can be identified in a specific cell population and each of them can bear a different function (5,14,15) or play a specific role in the development of diseases (16)(17)(18)(19)(20). A general approach to the visualization of flow cytometric data is the utilization of bivariate plots.…”

“…Currently, thanks to upcoming technologies and to the availability of new, bright fluorochromes such as tandem conjugates and quantum dots, it is possible to stain cells with up to 17 colors simultaneously (5). Theoretically, considering only the antigens that are clearly expressed or not in a given cell, such a large number of fluorescence signals would allow for the identification of 2 17 different cell populations in a few microliter of blood. Clearly, the analysis of results deriving from such a large number of antigen combinations is not feasible with classical approaches, i.e.…”

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

“…Indeed, in a number of diseases CD4 1 CD28 À T cells have been shown to infiltrate into the main target organ and their presence mirrors disease activity [3,6,7]. Typical characteristics of CD4 1 CD28 À T cells are a restricted TCR repertoire, rapid secretion of IFN-g and TNF, cytotoxic activity, and CD57 expression indicative of a highly differentiated phenotype [8][9][10].…”

Clinical flow cytometry, a hypothesis‐driven discipline of modern cytomics

“…However, these investigations are poised to sort out the minute details of immunoregulatory disorders in infections such as HIV (57) and in animal and human genetic disorders such as the defects of the newly discovered regulatory CD4 ϩ T cells (58,59).…”