Donor Ethnicity Influences Outcomes following Deceased-Donor Kidney Transplantation in Black Recipients

Although the majority of deceased-donor kidneys are donated after brain death, increased recovery of kidneys donated after cardiac death could reduce the organ shortage and is now a national priority. Racial disparities in donations after brain death have been well described for renal transplantation, but it is unknown whether similar disparities occur in donations after cardiac death. In this study, outcomes of adult deceased-donor renal transplant recipients included in the United Network for Organ Sharing database (1993 through 2006) were analyzed. Among black recipients of kidneys obtained after cardiac death, those who received kidneys from black donors had better long-term graft and patient survival than those who received kidneys from white donors. In addition, compared with standard-criteria kidneys from white donors after brain death, kidneys from black donors after cardiac death conferred a 70% reduction in the risk for graft loss (adjusted hazard ratio 0.30; 95% confidence interval 0.14 to 0.65; P = 0.002) and a 59% reduction in risk for death (adjusted hazard ratio 0.41; 95% confidence interval 0.2 to 0.87; P = 0.02) among black recipients. These findings suggest that kidneys obtained from black donors after cardiac death may afford the best long-term survival for black recipients

Cross-reactive microbial peptides do not expand HIV-1-specific CD8⁺ T cells in HIV-negative donors.

<p>25 HIV-negative HLA-B*27⁺ donors were screened for the presence of KK10-specific CD8⁺ T cells. Donor PBMCs were stimulated with KK10 peptide, KK10CR peptides or negative control CEF pooled peptides for six days, and the percentage of (<b>A</b>) KK10-specific and (<b>B</b>) IFN-γ⁺Perforin⁺ CD8⁺ T cells was quantified by flow cytometry.</p

CD8⁺ T cells stimulated with cross-reactive microbial peptides can suppress HIV-1 infection.

<p>Purified CD4⁺ T cells from three HIV-1-positive HLA-B*27⁺ subjects were spinoculated with single-round NL4-3 GFP reporter virus and then co-cultured with peptide-stimulated or unstimulated (fresh <i>ex vivo</i>) autologous CD8⁺ T cells. Viral suppression was measured at four different effector-to-target cell ratios. Left panels show suppression of wild-type (WT) NL4-3 reporter virus, and right panels show suppression of NL4-3 harboring the R264K and L268 mutations in KK10, which prevent KK10 presentation on HLA-B*27 MHC molecules.</p

Characteristics of HIV-infected patients.

<p>Characteristics of HIV-infected patients.</p

KK10 and KK10-cross-reactive microbial peptides differentially expand KK10-specific CD8⁺ T cells.

<p>(<b>A</b>) IFN-y release by ELISpot from HIV-positive HLA-B*27⁺ subject PBMCs stimulated with dilutions of KK10 or KK10CR peptides. (<b>B</b>) Characterization of KK10-specific TCR repertoires after PBMC stimulation with KK10 or KK10CR peptides. PBMCs from HIV-1-positive HLA-B*27⁺ subjects were stimulated with peptides for six days, and KK10-specific CD8⁺ T cells were sorted from fresh (unstimulated), KK10-stimulated, or KK10CR-stimulated PBMCs. Frequencies of unique TCR clones as measured by diversity in the TCR-β CDR3 region were quantified by ImmunoSEQ deep sequencing. Each dot shows the frequency of a single TCR clone in the specified KK10-specific CD8⁺ T cell populations. TCR clones that have the same frequency in both populations compared on a plot fall on the diagonal line. Magenta dots indicate TCR clones that are present at significantly different frequencies (minimum 20 reads in either condition, p<0.005, Fisher’s Exact test with Benjamini-Hochberg correction. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192098#pone.0192098.s001" target="_blank">S1 Table</a> shows all associated p-values).</p

Panel of potential SL9 cross-reactive peptides.

<p>Panel of potential SL9 cross-reactive peptides.</p

SL9 and SL9-cross-reactive microbial peptides differentially expand SL9-specific CD8⁺ T cells.

<p>Characterization of SL9-specific TCR repertoires after PBMC stimulation with SL9 or SL9CR peptides. PBMCs from HIV-1-positive HLA-A2⁺ subjects were stimulated with peptides for six days, and SL9-specific CD8⁺ T cells were sorted from fresh (unstimulated), SL9-stimulated, or SL9CR-stimulated PBMCs. Frequencies of unique TCR clones as measured by diversity in the TCR-β CDR3 region were quantified by ImmunoSEQ deep sequencing. Each dot shows the frequency of a single TCR clone in the specified SL9-specific CD8⁺ T cell populations. TCR clones that have the same frequency in both populations compared on a plot fall on the diagonal line. Magenta dots indicate TCR clones that are present at significantly different frequencies (minimum 20 reads in either condition, p<0.005, Fisher’s Exact test with Benjamini-Hochberg correction. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192098#pone.0192098.s002" target="_blank">S2 Table</a> shows all associated p-values).</p

PBMCs stimulated with cross-reactive microbial peptides can suppress HIV-1 infection.

<p>(<b>A-B</b>) Results of PBMC suppression assay. PBMCs from HIV-1-positive HLA-B*27⁺ subjects were stimulated for five days with no peptide, CEF pooled peptides, KK10 peptide, or KK10CR peptide and then infected with highly concentrated IIIB virus. After 40 hours, infection of CD3⁺/CD8^- cells was measured by staining for intracellular HIV-1 Gag. Values below 20% (in grey) fall below the limit of quantification. Part <b>A</b> shows flow cytometric results for subject ES31; part <b>B</b> shows summarized results for five subjects with CEF pooled peptides, KK10 peptide, and individual KK10CR peptides (<b>C-D</b>) PBMCs from HIV-1-positive HLA-A2⁺ subjects were stimulated for five days with no peptide, CEF pooled peptides, SL9 peptide, or SL9CR peptide and then infected with highly concentrated IIIB virus. After 40 hours, infection of CD3⁺/CD8^- cells was measured by staining for intracellular HIV-1 Gag. Part <b>C</b> shows flow cytometric results for subject CP37; part <b>D</b> shows summarized results for seven subjects with CEF pooled peptides, SL9 peptide, and individual SL9CR peptides.</p