CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants

Cayota, Alfonso; Vuillier, Françoise; González, Gustavo; Dighiero, Guillaume

doi:10.1046/j.1365-2249.1996.d01-652.x

Cited by 17 publications

(6 citation statements)

References 37 publications

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“…production of HXB-LUC particles. These results have also been previously reported by other groups using primary naive T cells in vivo (16,18,20,22,54). Also, syncytium formation in HIV-1-infected cells occurred exclusively in CD45RO T cells activated by anti-CD3/anti-CD28 treatment.…”

Section: Higher Hiv-1 Ltr Activation and Hiv-1 Replication In Cd45ro-supporting

confidence: 90%

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Robichaud

Barbeau

Fortin

et al. 2002

Journal of Biological Chemistry

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Human immunodeficiency virus type-1 (HIV-1) preferentially replicates in CD4-expressing T cells bearing a "memory" (CD45RO؉) rather than a "naive" (CD45RA؉/ CD62L؉) phenotype. Yet the basis for the higher susceptibility of these cells to HIV-1 infection remains unclear. Because the nature of the CD45 isoform itself can affect biochemical events in T cells, we set out to determine whether these isoforms could differently modulate HIV-1 long terminal repeat (LTR) activity and thereby replication. Through the use of CD4؉ Jurkat T cells specifically expressing distinct CD45 isoforms (i.e. CD45RABC or CD45RO), we demonstrated that a difference in CD45 isoform expression conferred preferential replication of HIV-1 to CD45RO-expressing T cell clones following a physiological CD3/CD28 stimulation. Closer analysis indicated that higher HIV-1 LTR activation levels were consistently observed in CD45RO-positive cells, which was paralleled by more pronounced nuclear factor of activated T cells (NFAT) activation in these same cells. Specific involvement of NFAT1 was revealed in studied Jurkat clones by mobility shift analyses. In addition, preferential activation of the LTR and viral replication in CD45RO T cells was FK506-and cyclosporin A-sensitive. These results underscore the importance of NFAT in HIV-1 regulation and for the first time identify the role of the CD45 isoform in limiting productive HIV-1 replication to the human CD4 memory T cell subset.

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Section: Higher Hiv-1 Ltr Activation and Hiv-1 Replication In Cd45ro-supporting

confidence: 90%

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Robichaud

Barbeau

Fortin

et al. 2002

Journal of Biological Chemistry

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“…Furthermore, the sensitivity of tyrosine phosphatases to intracellular thiol status has been shown to be important in regulating the immune response (40,41). For example, a GSH deficiency in HIV-infected CD4 + T cells impaired tyrosine phosphatase activity, which could be restored by the presence of NAC (42). The system is no doubt a complicated one, and future studies would require the simultaneous examination of several cell types and their relative roles as well as how their signaling pathways could be affected by GSH concentrations.…”

Section: Discussionmentioning

confidence: 99%

Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria

Tan

Lee²,

Low³

et al. 2012

J. Clin. Invest.

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Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12-IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast,

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“…Since previous studies have suggested that HIV-1 infection impaired CD45 cell surface expression or PTP activity (66,98,99), it can be postulated that if a similar in vivo regulation of NFAT activation by CD45 occurs, it hence follows that CD4 ϩ T cells impaired in their CD45 PTP activity might be more prone to HIV-1 LTR activation upon TCR-independent stimulation. For instance, pathways activated by RANTES or the transmembrane activator and cAML interaction, CD43, and CD2 cell surface molecules have all been shown to culminate into calcium mobilization and NFAT activation in T cells (100 -103) and might be such examples.…”

Section: Discussionmentioning

confidence: 99%

Negative Regulation of the NFAT1 Factor by CD45: Implication in HIV-1 Long Terminal Repeat Activation

Barbeau

Robichaud

Fortin

et al. 2001

The Journal of Immunology

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HIV-1 gene regulation is greatly dependent on the presence of the −104/−81 enhancer region which is regulated by both NF-κB and NFAT transcription factors. We have found that a greater induction in HIV-1 long terminal repeat-driven gene expression was observed upon PMA/ionomycin (Iono) stimulation of a CD45-deficient cell line (J45.01) in comparison to the parental Jurkat cells. Unlike NF-κB which was not affected by the absence of CD45, NFAT showed a much greater augmentation in nuclear translocation and transcriptional activity in J45.01 cells upon PMA/Iono stimulation. PMA/Iono-induced NFAT activation, NFAT translocation and calcium influx peaked at similar time points for both Jurkat and J45.01 cell lines. The NFAT-dependent promoters from the IL-2 and TNF-α genes were also more potently activated by PMA/Iono in J45.01 cells. Interestingly, higher levels of intracellular calcium were consistently demonstrated in PMA/Iono-induced CD45-deficient cell lines (J45.01 and HPB45.0). Furthermore, PMA/Iono induction of calcium mobilization in both Jurkat and J45.01 cell lines was observed to be EGTA-sensitive. Mechanistic studies revealed that CD3ζ and ZAP-70 were more heavily tyrosine phosphorylated in J45.01 cells than Jurkat cells. Analysis of the HIV-1 enhancer by EMSAs demonstrated that the bound NFAT complex was present at higher levels in J45.01 nuclear extracts and that the NFAT1 member was predominant. In conclusion, our results indicate that NFAT activation by stimuli acting in a more distal fashion from the TCR-mediated signaling pathway can be down-regulated by CD45 and that this CD45-dependent regulation in turn affects HIV-1 long terminal repeat activation.

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CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants

Cited by 17 publications

References 37 publications

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria

Negative Regulation of the NFAT1 Factor by CD45: Implication in HIV-1 Long Terminal Repeat Activation

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