Role of CD25+ and CD25-T cells in acute HIV infection in vitro.

Abstract

T cell activation plays a major role in the ability of the HIV to remain latent or establish a productive infection. The alpha-chain of the IL-2R (CD25, Tac, p55) is expressed on activated but not resting T cells and therefore represents an ideal marker to distinguish activated from resting T cells. The present studies were designed to define the role of CD25+ (activated) and CD25- (resting) T cells in an acute HIV infection in vitro. This objective was accomplished by selectively killing CD25+ cells with an anti-CD25-ricin A chain immunotoxin (RFT5-deglycosylated ricin A (dgA)) either before or after HIV infection, and then determining the effect of eliminating these cells on the secretion of viral p24 Ag. Three major findings have emerged from this study: 1) Elimination of the small population (3 to 5%) of activated, CD25+ cells present in normal PBMC before HIV infection results in a 99% reduction in p24 secretion. 2) RFT5-dgA, an immunotoxin directed against CD25, kills HIV-infected CD25+ cells. Elimination of the CD25+ cells after infection with HIV virtually stops viral production and the spread of the infection in these cultures. This was confirmed by coculturing RFT5-dgA-treated PBMC with H9 cells. 3) When RFT5-dgA-treated PBMC (CD25-cells) were infected with HIV and then activated with a solid phase anti-CD3 mAb, the levels of p24 produced were comparable with those of PBMC from which the CD25+ cells had not been eliminated. Taken together these findings suggest that both activated (CD25+) and resting/quiescent (CD25-) cells can be infected with HIV but that only the CD25+ cells produce viral proteins in the absence of additional activation.

Nicotinamide mononucleotide impacts HIV-1 infection by modulating immune activation in T lymphocytes and humanized mice

“…CD25 is also known as IL-2 receptor. 49 To further investigate if NMN could impact IL-2-induced T cell proliferation and HIV-1 replication, we measured CD25 + and ki67 + cell frequencies among NMN-treated HIV-1-infected CD4 + T cells in the presence of dose-escalating IL-2 on day 4 and day 7 after infection ( Supplementary Figure S8a ). We found that the frequencies of CD25 + and Ki67 + CD4 T cells did not change significantly by IL-2, but that decreased CD25 MFI and increased ki67 MFI were found on day 7 when compared to day 4 ( Supplementary Figure S8b ).…”

“…Our findings pointed to a selective effect of NMN on CD25 + CD4 + T cells. 49 By CyTOF analysis, CXCR3 + effector and CCR4 + central memory CD4 + T cells were found to be two distinguishable subsets affected by the NMN treatment in terms of the CD25 expression. These CXCR3 + effector and CCR4 + central memory CD4 + T cell subsets were of low expression of CCR6.…”

TRAIL (DR5) receptor and the modulation of TRAIL pathway in PLWHIV: key mechanisms in the progression of HIV disease.

“…al. through an in vitro assay shown a signi cant increase in CD25 in PLWHIV (50). By maintaining the expression of CD25, the virus ensures a productive infection (35), however in HIV infection where is perpetuated a repeated stimulation of CD4 + T-cells, also is favored an activation induced cell death (AICD) result of the co-expression of Fas and FasL (51).…”

Exposure to Secreted Bacterial Factors Promotes HIV-1 Replication in CD4 + T Cells

“…Our data show that Gag does not require CD25 to accumulate at the VS, which is consistent with data showing VS formation in CD25-negative cell lines. Interestingly, CD25 expression combined with other activation markers has been shown to predict HIV-1 permissiveness of CD4 + T cells ( 81 , 82 ). Further, regulatory T cells (Tregs), expressing high levels of CD25, have been shown to be susceptible to HIV-1 infection ( 82 – 84 ).…”

“…Interestingly, CD25 expression combined with other activation markers has been shown to predict HIV-1 permissiveness of CD4 + T cells ( 81 , 82 ). Further, regulatory T cells (Tregs), expressing high levels of CD25, have been shown to be susceptible to HIV-1 infection ( 82 – 84 ). Further analyses will elucidate if bacteria-induced CD25-high PBT have also a Treg phenotype.…”