CD4+CD8+ T cells represent a significant portion of the anti-HIV T cell response to acute HIV infection.

Previous studies have revealed that HIV-infected individuals possess circulating CD4(+)CD8(+) double-positive (DP) T cells specific for HIV Ags. In the present study, we analyzed the proliferation and functional profile of circulating DP T cells from 30 acutely HIV-infected individuals and 10 chronically HIV-infected viral controllers. The acutely infected group had DP T cells that showed more proliferative capability and multifunctionality than did both their CD4(+) and CD8(+) T cells. DP T cells were found to exhibit greater proliferation and higher multifunctionality compared with CD4 T cells in the viral controller group. The DP T cell response represented 16% of the total anti-HIV proliferative response and >70% of the anti-HIV multifunctional response in the acutely infected subjects. Proliferating DP T cells of the acutely infected subjects responded to all HIV Ag pools with equal magnitude. Conversely, the multifunctional response was focused on the pool representing Nef, Rev, Tat, VPR, and VPU. Meanwhile, the controllers' DP T cells focused on Gag and the Nef, Rev, Tat, VPR, and VPU pool for both their proliferative and multifunctional responses. Finally, we show that the presence of proliferating DP T cells following all HIV Ag stimulations is well correlated with proliferating CD4 T cells whereas multifunctionality appears to be largely independent of multifunctionality in other T cell compartments. Therefore, DP T cells represent a highly reactive cell population during acute HIV infection, which responds independently from the traditional T cell compartments.

1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization.

Expression of the vitamin D receptor (VDR) in the kidney and intestine plays a major role in calcium homeostasis and the metabolism of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Calcium and 1,25(OH)(2)D(3)-mediated regulation of renal and duodenal VDR expression has been analyzed in vivo and the mechanisms responsible for the renal regulation have been studied in mouse kidney TCMK-1 cells. Vitamin D-deficient mice were maintained on diets containing either 0.02 or 0.47% calcium, with or without 50ng of 1,25(OH)(2)D(3) per day. Renal VDR levels were significantly higher in the vitamin D-deficient mice fed the 0.47% calcium diet vs. the calcium-restricted diet, and were increased 5-fold by 1,25(OH)(2)D(3) when dietary calcium was present. The renal VDR transcript was expressed at a basal level in the absence of calcium or 1,25(OH)(2)D(3); 50ng of 1,25(OH)(2)D(3) elevated renal VDR mRNA levels approximately 10-fold in the presence of calcium. Neither calcium nor 1,25(OH)(2)D(3) had any significant effect on duodenal VDR or VDR mRNA expression. In TCMK-1 cells, 1,25(OH)(2)D(3) increased receptor and VDR mRNA content in both low and adequate calcium medium. The 1,25(OH)(2)D(3)-mediated increase in VDR mRNA did not result from increased stability of the transcript. Further, the increase in mRNA was blocked by cycloheximide, indicating a requirement for protein synthesis and an indirect regulation of VDR transcription. Thus, both dietary serum calcium and 1,25-(OH)(2)D(3) are required for VDR expression in kidney but not in intestine where neither is required. The 1,25-(OH)(2)D(3) requirement can also be shown in TCMK-1 cells in vitro, while the calcium requirement was not found.