Papers by Deborah Hendricks
CMV induces the expansion of a unique subset of human NK cells expressing high levels of the acti... more CMV induces the expansion of a unique subset of human NK cells expressing high levels of the activating CD94-NKG2C receptor that persist after control of the infection. We investigated whether this subset is CMV specific or is also responsive to acute infection with EBV. We describe a longitudinal study of CMV(-) and CMV(+) students who were acutely infected with EBV. The NKG2C(hi) NK subset was not expanded by EBV infection. However, EBV infection caused a decrease in the absolute number of immature CD56(bright)CD16(-) NK cells in the blood and, in CMV(+) individuals, induced an increased frequency of mature CD56(dim)NKG2A(+)CD57(+) NK cells in the blood that persisted into latency. These results provide further evidence that NKG2C(+) NK cells are CMV specific and suggest that EBV infection alters the repertoire of NK cells in the blood.
Journal of immunology (Baltimore, Md. : 1950), 2013
Trends in immunology, 2013
Immunological memory has traditionally been regarded as a unique feature of the adaptive immune r... more Immunological memory has traditionally been regarded as a unique feature of the adaptive immune response, mediated in an antigen-specific manner by T and B lymphocytes. All other hematopoietic cells, including natural killer (NK) cells, are classified as innate immune cells, which have been considered short-lived but can respond rapidly against pathogens in a manner not thought to be driven by antigen. Interestingly, NK cells have recently been shown to survive long term after antigen exposure and subsequently mediate antigenspecific recall responses. In this review, we address the similarities between, and the controversies surrounding, three major viewpoints of NK memory that have arisen from these recent studies: (i) mouse cytomegalovirus (MCMV)-induced memory; (ii) cytokine-induced memory; and (iii) liver-restricted memory cells.
Nature immunology, 2012
Using whole-genome microarray datasets of the Immunological Genome Project, we demonstrate a clos... more Using whole-genome microarray datasets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK and T cells than any other leukocytes, distinguished by their expression of similar signaling functions. While resting NK cells were known to share expression of a few genes with cytotoxic CD8 + T cells, transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many with unknown functions. The NK cell response to viral infection is dampened relative to cytotoxic CD8 + T cells, in part due to their "pre-primed" state. Collectively, the data provide global context for known and novel molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.
Nature Reviews Immunology, 2011
T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting... more T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.
Blood, 2011
After intrathymic development, T cells exit the thymus and join the peripheral T-cell pool. Such ... more After intrathymic development, T cells exit the thymus and join the peripheral T-cell pool. Such recent thymic emigrants (RTEs) undergo both phenotypic and functional maturation during the first 3 weeks they reside in the periphery. Using a well-controlled in vitro polarization scheme, we now show that CD4(+) RTEs are defective in T-helper (Th) type 0 (Th0), Th1, Th17, and regulatory T-cell lineage commitment, with dampened cytokine production and transcription factor expression. In contrast, CD4(+) RTES are biased toward the Th2 lineage both in vitro and in vivo, with more robust interleukin-4, interleukin-5, and interleukin-13 production than their mature naive counterparts. Coculture experiments demonstrate that mature naive T cells influence neighboring RTEs in their Th responses. In adoptive hosts, CD4(+) RTEs drive production of the Th2-associated antibody isotype immunoglobulin G1 and mediate airway inflammatory disease. This bias in RTEs likely results from dampened negative regulation of the Th2 lineage by diminished levels of T-bet, a key Th1 transcription factor. CD4(+) RTEs thus represent a transitional population with a distinct interpretation of, and response to, immunologic cues. These characteristics may be beneficial during the postthymic maturation period by leading to the avoidance of inappropriate immune responses, particularly in lymphopenic neonates and adults.
Journal of immunology (Baltimore, Md. : 1950), 2009
Proceedings of The National Academy of Sciences, 2009
Complete T cell development requires postthymic maturation, and we investigated the influence of ... more Complete T cell development requires postthymic maturation, and we investigated the influence of this ontological period on the CD8 T cell response to infection by comparing responses of mature CD8 T cells with those of recent thymic emigrants (RTEs). When activated with a noninflammatory stimulus or a bacterial or viral pathogen, CD8 RTEs generated a lower proportion of cytokine-producing effector cells and long-lived memory precursors compared with their mature counterparts. Although peripheral T cell maturation is complete within several weeks after thymic egress, RTE-derived memory cells continued to express inappropriate levels of memory cell markers and display an altered pattern of cytokine production, even 8 weeks after infection. When rechallenged, RTE-derived memory cells generated secondary effector cells that were phenotypically and functionally equivalent to those generated by their mature counterparts. The defects at the effector and memory stages were not associated with differences in the expression of T cell receptor-, costimulation-, or activation-associated cell surface markers yet were associated with lower Ly6C expression levels at the effector stage. This work demonstrates that the stage of postthymic maturation influences cell fate decisions and cytokine profiles of stimulated CD8 T cells, with repercussions that are apparent long after cells have progressed from the RTE compartment.
European journal of immunology, 2007
Microorganisms with pathogen-associated molecular patterns (PAMP) activate B cells directly by bi... more Microorganisms with pathogen-associated molecular patterns (PAMP) activate B cells directly by binding to TLR and also indirectly by inducing APC to release cytokines such as BAFF that promote B cell survival. We found that murine B cells activated concomitantly with LPS (TLR-4 ligand) and BAFF are protected from spontaneous apoptosis, but are more susceptible to Fas/CD95-mediated cell death. This increased susceptibility to Fas-induced apoptosis is associated with a dramatic coordinated upregulation of Fas/CD95 and IRF-4 expression through a mechanism mediated, at least in part, by inhibition of the MEK/ERK pathway.
New England Journal of Medicine, 2009
We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with sp... more We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1. NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes.
Update on Cancer Therapeutics, 2006
In recent years, the feasibility of isolating and expanding antigen-specific T cells for use in c... more In recent years, the feasibility of isolating and expanding antigen-specific T cells for use in clinical trials has been established by several laboratories. The fundamental considerations associated with isolation or enrichment of antigen-specific effector cells in vitro, and the ...
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Papers by Deborah Hendricks