Explore the vast range of titles available.

Effector cells derived from central memory CD8⁺ T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting that they are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacy of effector cells derived from naïve T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naïve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specific T-cell receptor. We found that naïve, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naïve T cells lost the expression of CD62L more rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminal differentiation and replicative senescence. Consistent with this KLRG-1⁻ phenotype, naïve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptive transfer. These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8⁺ T cells may allow superior efficacy upon adoptive transfer.

Effector cells derived from central memory CD8 super(+) T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting thatthey are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacyof effector cells derived from naoe¯ve T cells. We sought to investigate the efficacy of tumor-specific effector cells derivedfrom naoe¯ve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specificT-cell receptor. We found that naoe¯ve, rather than central memory T cells, gave rise to an effector population that mediatedsuperior antitumor immunity upon adoptive transfer. Effector cells developed from naoe¯ve T cells lost the expression of CD62Lmore rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminaldifferentiation and replicative senescence. Consistent with this KLRG-1 super(-) phenotype, naoe¯ve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptivetransfer. These results indicate that insertion of genes that confer antitumor specificity into naoe¯ve rather than centralmemory CD8 super(+) T cells may allow superior efficacy upon adoptive transfer.

Effector cells derived from central memory CD8⁺ T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting that they are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacy of effector cells derived from naïve T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naïve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specific T-cell receptor. We found that naïve, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naïve T cells lost the expression of CD62L more rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminal differentiation and replicative senescence. Consistent with this KLRG-1⁻ phenotype, naïve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptive transfer. These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8⁺ T cells may allow superior efficacy upon adoptive transfer.

Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)—based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38 + /HLA-DR + ) for CD4 + and CD8 + lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART.