Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination

Masopust, David; Ha, Sang Jun; Vezys, Vaiva; Ahmed, Rafi

doi:10.4049/jimmunol.177.2.831

Cited by 286 publications

(405 citation statements)

References 69 publications

(64 reference statements)

Supporting

Mentioning

348

Contrasting

Unclassified

Order By: Relevance

“…Some markers resembled those of T EM cells, which have been identified for successive infections (25)(26)(27)(28)(29)(30), rather than central memory (T CM ) cells, which are favored by antigens that are cleared (31). Nevertheless, unlike T EM , the reactive populations we detected were found in lymph nodes, where T CM cells preferentially reside, and most of these proliferating cells expressed the selectin CD62L that is also expressed on T CM cells and directs migration to lymph nodes.…”

Section: Surface; This Was Verified By Transferring T Cells Into Rag1mentioning

confidence: 62%

Adaptive immunity to murine skin commensals

Shen¹,

Li²,

Hixon³

et al. 2014

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

View full text Add to dashboard Cite

Significance Barrier function of the skin in blocking microbial invasion has been attributed to the structural integrity of the epithelium, augmented by innate immune mechanisms. T cells and antigen-presenting cells have long been observed in the skin, but what is their role? Here we report, for the first time, that commensal skin bacteria are recognized by major populations of T cells in skin-draining lymph nodes of mice. We report a previously unrecognized role for T cells in preventing breach of the skin epithelial barrier by certain species of commensal bacteria, especially mycobacteria, and we examine the mechanism. Patients deficient in T cells frequently show infectious cutaneous manifestations and mycobacterial susceptibility, reflecting features of our study in mice.

show abstract

Section: Surface; This Was Verified By Transferring T Cells Into Rag1mentioning

confidence: 62%

Adaptive immunity to murine skin commensals

Shen¹,

Li²,

Hixon³

et al. 2014

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

View full text Add to dashboard Cite

show abstract

“…Future studies may focus on using adenoviral vectors with alternate mucosal delivery routes such as intranasal, vaginal, and rectal immunization [43] or further characterization of the mucosal response upon systemic administration, particularly in the effector compartments of the lamina propria [44] or the intestinal epithelium. There have been heterologous prime-boost studies done with chimpanzee-derived adenoviral vectors [45] as well as other viruses and vectors [46] to drive an increase of effector memory CD8 + T cell population in the gut. Heterologous prime-boosting through the i.m.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut

Lin

Cun

Harris-McCoy

et al. 2007

Vaccine

View full text Add to dashboard Cite

Gut-associated lymphoid tissue (GALT) is the primary replication site for HIV-1, resulting in a pronounced CD4 + T cell loss in this tissue during primary infection. A mucosal vaccine that generates HIV-specific CD8 + T cells in the gut could prevent the establishment of founder populations and broadcasting of virus. Here, we immunized mice orally and systemically with a chimpanzee derived adenoviral vector expressing HIV gag (AdC68gag) and measured frequencies of gag-specific interferon-gamma (IFN-γ) producing CD8 + T cells in the GALT. A single oral administration was inefficient at eliciting responses in the mesenteric lymph nodes and Peyer's Patches, while a single intramuscular administration elicited strong systemic and detectable mucosal responses. The gagspecific CD8 + T cell responses were present in both acute and memory phases following intramuscular administration.

show abstract

“…However, effector CD8 T cells are a heterogeneous population composed of cells with varying intrinsic potential for survival and differentiation into memory cells (3,7,8). During several types of infections [such as lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), Listeria monocytogenes, and Toxoplasma gondii], most of the effector CD8 T cells terminally differentiate and become short-lived, but a minority maintain memory potential and are capable of self-renewal (9)(10)(11)(12)(13)(14). Separation of these subsets is possible because most memory precursor cells express higher amounts of IL-7Rα, CD27, and CXCR3 and lower amounts of KLRG1, whereas shorter-lived effector cells express these receptors in a reciprocal pattern (3,10,13,15).…”

mentioning

confidence: 99%

Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival

Hand

Cui²,

Jung³

et al. 2010

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

191

View full text Add to dashboard Cite

During viral infection, effector CD8 T cells contract to form a population of protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that control effector cell death during infection are poorly understood. We investigated how short-and long-lived antiviral CD8 T cells differentially used the survival and cell growth pathways PI3K/AKT and JAK/STAT5. In response to IL-15, long-lived memory precursor cells activated AKT significantly better than shortlived effector cells. However, constitutive AKT activation did not enhance memory CD8 T-cell survival but rather repressed IL-7 and IL-15 receptor expression, STAT5 phosphorylation, and BCL2 expression. Conversely, constitutive STAT5 activation profoundly enhanced effector and memory CD8 T-cell survival and augmented homeostatic proliferation, AKT activation, and BCL2 expression. Taken together, these data illustrate that effector and memory cell viability depends on properly balanced PI3K/AKT signaling and the maintenance of STAT5 signaling.apoptosis | cytokine signaling | interleukin 15 | interleukin 7 | lymphocytic choriomeningitis virus M emory CD8 T cells form from a much larger effector population and provide long-term immunity against subsequent infections via rapid reactivation. The exact biochemical mechanism governing the survival of memory cells and apoptosis of the majority of effector cells is not well understood (1). As naïve T cells differentiate into effector and memory T cells, cytokines play a key role in their differentiation and survival. IL-2, IL-7, and IL-15 promote the expansion and survival of activated T cells (2). As memory CD8 T cells form following acute viral infection, two of these cytokines, IL-15 and IL-7, direct memory T cell survival and homeostasis (3, 4). Downstream of their specific receptors, IL-7 and IL-15 activate two primary pathways: janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) and phosphoinositide 3-kinase (PI3K)/AK-transforming (AKT). Activation of these two pathways results in decreased levels of proapoptotic proteins, increased expression of antiapoptotic genes such as BCL2, and activation of cellular growth and proliferation pathways regulated by mTOR and cyclins (5). The balance between these pro-and antiapoptotic factors controls the survival of CD8 T cells after immunization (6).Early models predicted that effector CD8 T-cell contraction was a result of deprivation of T-cell growth factor cytokines that wane during the later stages of infection and that survival was determined via the stochastic interaction of effector T cells with these cytokines. However, effector CD8 T cells are a heterogeneous population composed of cells with varying intrinsic potential for survival and differentiation into memory cells (3,7,8). During several types of infections [such as lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), Listeria monocytogenes, and Toxoplasma gondii], most of the effector CD8 T cells terminally differentiate and become short-lived, but ...

show abstract

Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination

Cited by 286 publications

References 69 publications

Adaptive immunity to murine skin commensals

Adaptive immunity to murine skin commensals

Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut

Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival

Contact Info

Product

Resources

About