Improvement in Aids Patients on Peptide T

Bridge, T. Peter; Heseltine, Peter N. R.; Parker, E.E.; Eaton, Elaine M.; Ingraham, LoringJ.; Gill, Mark A.; Ruff, Michael R.; Pert, C.B.; Goodwin, F. K.

doi:10.1016/s0140-6736(89)90416-9

Cited by 30 publications

(2 citation statements)

References 5 publications

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“…Eight micrograms of DAPTA (TOCRIS), a specific antagonist of CCR5 (24–26), was injected subcutaneously into the ventral surface of the ears 2.5 days following DNFB challenge. Immediately after DAPTA treatment, ear cells were photoconverted by violet light as described above.…”

Section: Methodsmentioning

confidence: 99%

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin

et al. 2019

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Regulatory T cells (Tregs) migrate between lymphoid and peripheral tissues for maintaining immune homeostasis. Tissue-specific function and functional heterogeneity of Tregs have been suggested, however, correlation between them and inter-tissue movement remain unknown. We used a contact hypersensitivity model of mice expressing a photoconvertible protein for tracking migratory cells. After marking cells in skin, we purified Tregs exhibiting a different migration pattern [Tregs recruiting to or remaining in the skin and emigrating from the skin to draining lymph nodes (dLNs) within half a day] and examined single-cell gene and protein expression profiles. Correlation and unsupervised clustering analyses revealed that Tregs in both skin and dLNs comprised two subpopulations, one highly expressing Nrp1 with variable CD25, Granzyme B, and/or CTLA-4 expression and another with 3 subsets strongly expressing CD25, Granzyme B, or CTLA-4 together with CD39. Characteristic subsets of Tregs remaining in the skin displayed higher CD25 and CD39 expression and lower Granzyme B and CTLA-4 expression compared with Tregs migrating to the skin. In addition, CCR5 expression in Tregs in skin was positively and negatively correlated with CD39 and Nrp-1 expression, respectively. To assess the predictive value of these data for immunotherapy, we blocked CCR5 signaling and found modest downregulation of CD39 and modest upregulation of Nrp1 expression in skin Tregs. Our data reveal a high functional diversity of Tregs in skin that is strongly related to trafficking behavior, particularly skin retention. Modulation of tissue-specific trafficking and function is a promising clinical strategy against autoimmune, infectious, and neoplastic diseases. Significance Statement Regulatory T cells (Tregs) are essential for maintaining immune homeostasis. To reveal tissue-specific immunoinhibitory functions and inter-tissue movement correlation based on Treg functional heterogeneity, we examined single-cell gene and protein expression profiles of Tregs recruited to, remaining in, or emigrating from the contact hypersensitivity-induced inflamed skin. Tregs in skin were composed of several subpopulations; one with high Nrp1 expression and another with 3 subsets strongly expressing CD25, Granzyme B, or CTLA-4 together with CD39. Tregs remaining in skin displayed highCD25, CD39, and CCR5 expression, and CCR5 signaling blockade downregulated CD39. A high Treg functional diversity in skin is strongly related to trafficking behavior. Tissue-specific trafficking and functional modulation are a promising clinical strategy against autoimmune, infectious, and neoplastic diseases.

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Section: Methodsmentioning

confidence: 99%

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin

et al. 2019

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“…Key words: cAMP dependent protein kinases/gp120 protein/peptide T/psoriasis. J Invest Dermatol 110:332-337, 1998 improvement of the psoriatic lesions are of interest (Wetterberg et al, 1987;Duvic et al, 1987bDuvic et al, , 1994Bridge et al, 1989;Townsend et al, 1995). More recent studies performed on psoriatic patients confirmed the beneficial effects of peptide T on this disease (Marcusson et al, , 1991Marcusson and Wetterberg, 1989;Farber et al, 1991;Delfino et al, 1992;Talme et al, 1995).…”

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confidence: 99%

Effects of [D-Ala1] Peptide T-NH2 and HIV Envelope Glycoprotein Gp120 on Cyclic AMP Dependent Protein Kinases in Normal and Psoriatic Human Fibroblasts

Liapi

Takahashi

Raynaud

et al. 1998

Journal of Investigative Dermatology

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In addition to acquired immunodeficiency syndrome (AIDS), persons infected with human immunodeficiency virus often develop cutaneous manifestations, including severe psoriasis. In previous studies, we have established that psoriatic fibroblasts and erythrocytes obtained from psoriatic patients exhibit decreased levels of cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA) activity and of 8-azido-[32P]cAMP binding to the RI and RII regulatory subunits of PKA. Because treatment of patients with peptide T (an octapeptide sequence found in the human immunodeficiency virus envelope glycoprotein gp120) has been observed to result in an improvement in the psoriatic condition, studies were initiated to determine if peptide T and gp120 protein treatment of normal and psoriatic human fibroblasts resulted in any changes in PKA. Exposure of psoriatic fibroblasts to peptide T resulted in a time (4 h to 6 d) and dose [10(-14)-10(-8) M] dependent increase in the levels of 8-azido-[32P]cAMP binding to the RI and RII regulatory subunits of PKA, along with a corresponding increase in PKA activity. Peptide T exhibited a biphasic dose dependent response, with maximal effects on PKA noted at 10(-12)M peptide T. Treatment of normal human fibroblasts with peptide T did not result in any change in PKA levels. Conversely, treatment of normal human fibroblasts for 18 h with gp120 protein [10(-13) M] resulted in a significant decrease in the levels of 8-azido-[32P]cAMP binding to RI and RII and in PKA activity. The presence of peptide T blocked this effect of the gp120 protein. These results indicate that peptide T and gp120 protein may inversely alter the intracellular levels of 8-azido-[32P]cAMP binding to RI and RII, and of PKA activity in susceptible cells. These observed changes in the cyclic AMP-PKA signaling pathway, a biochemical marker for psoriasis, may offer some mechanistic insight into the noted beneficial effects of peptide T treatment, including an improvement in psoriatic lesions.

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Randomized Double-blind Placebo-Controlled Trial of Peptide T for HIV-Associated Cognitive Impairment

Heseltine

Goodkin²,

Atkinson³

et al. 1998

Arch Neurol

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Improvement in Aids Patients on Peptide T

Cited by 30 publications

References 5 publications

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin

Effects of [D-Ala1] Peptide T-NH2 and HIV Envelope Glycoprotein Gp120 on Cyclic AMP Dependent Protein Kinases in Normal and Psoriatic Human Fibroblasts

Randomized Double-blind Placebo-Controlled Trial of Peptide T for HIV-Associated Cognitive Impairment

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