CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production

被引:99
作者
Peperzak, Victor [1 ]
Xiao, Yanling [1 ]
Veraar, Elise A. M. [1 ]
Borst, Jannie [1 ]
机构
[1] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands
关键词
CD8(+) T-CELL; COSTIMULATORY LIGAND CD70; CLONAL EXPANSION; DENDRITIC CELLS; MEMORY; STIMULATION; EXPRESSION; RESPONSES; RECEPTOR; GENERATION;
D O I
10.1172/JCI40178
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Immunity to infections relies on clonal expansion of CD8(+) T cells, their maintenance as effector CTLs, and their selection into a memory population. These processes rely on delivery of survival signals to activated CD8(+) T cells. We here reveal the mechanism by which costimulatory CD27-CD70 interactions sustain survival of CD8(+) effector T cells in infected tissue. By unbiased genome-wide gene expression analysis, we identified the Il2 gene as the most prominent CD27 target gene in murine CD8(+) T cells. In vitro, CD27 directed IL-2 expression and promoted clonal expansion of primed CD8+ T cells exclusively by IL-2-dependent survival signaling. In mice intranasally infected with influenza virus, Cd27(-/-) CD8(+) effector T cells displayed reduced IL-2 production, accompanied by impaired accumulation in lymphoid organs and in the lungs, which constitute the tissue effector site. Reconstitution of Cd27(-/-) CD8(+) T cells with the IL2 gene restored their accumulation to wild-type levels in the lungs, but it did not rescue their accumulation in lymphoid organs. Competition experiments showed that the IL-2 produced under the control of CD27 supported effector CD8(+) T cell survival in the lungs in an autocrine manner. We conclude that CD27 signaling directs the IL-2 production that is reportedly essential to sustain survival of virus-specific CTLs in nonlymphoid tissue.
引用
收藏
页码:168 / 178
页数:11
相关论文
共 49 条
[31]   CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression [J].
Matter, Matthias S. ;
Claus, Christina ;
Ochsenbein, Adrian F. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (07) :1847-1856
[32]   CD27 expression promotes long-term survival of functional effector-memory CD8+ cytotoxic T lymphocytes in HIV-infected patients [J].
Ochsenbein, AF ;
Riddell, SR ;
Brown, M ;
Corey, L ;
Baerlocher, GM ;
Lansdorp, PM ;
Greenberg, PD .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (11) :1407-1417
[33]   Stimulation by soluble CD70 promotes strong primary and secondary CD8+ cytotoxic T cell responses in vivo [J].
Rowley, TF ;
Al-Shamkhani, A .
JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :6039-6046
[34]   Priming of CD8+ T cell responses by pathogens typically depends on CD70-mediated interactions with dendritic cells [J].
Schildknecht, Anita ;
Miescher, Iris ;
Yagita, Hideo ;
van den Broek, Maries .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (03) :716-728
[35]   Cytokine control of memory T-cell development and survival [J].
Schluns, KS ;
Lefrançois, L .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (04) :269-279
[36]  
SMITH KA, 1989, ANNU REV CELL BIOL, V5, P397
[37]   The costimulation-regulated duration of PKB activation controls T cell longevity [J].
Song, JX ;
Salek-Ardakani, S ;
Rogers, PR ;
Cheng, M ;
Van Parijs, L ;
Croft, M .
NATURE IMMUNOLOGY, 2004, 5 (02) :150-158
[38]   Tolerogenic dendritic cells [J].
Steinman, RM ;
Hawiger, D ;
Nussenzweig, MC .
ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :685-711
[39]   Cutting edge: A critical role for CD70 in CD8 T cell priming by CD40-licensed APCs [J].
Taraban, VY ;
Rowley, TF ;
Al-Shamkhani, A .
JOURNAL OF IMMUNOLOGY, 2004, 173 (11) :6542-6546
[40]   Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions [J].
Tesselaar, K ;
Arens, R ;
van Schijndel, GMW ;
Baars, PA ;
van der Valk, MA ;
Borst, J ;
van Oers, MHJ ;
van Lier, RAW .
NATURE IMMUNOLOGY, 2003, 4 (01) :49-54