REGULATION AND FUNCTIONS OF INTERLEUKIN-2 RECEPTORS ON NORMAL AND HTLV-I-INFECTED HUMAN T LYMPHOCYTES NLM AIDSLINE Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


REGULATION AND FUNCTIONS OF INTERLEUKIN-2 RECEPTORS ON NORMAL AND HTLV-I-INFECTED HUMAN T LYMPHOCYTES

Diss Abstr Int [B]; 51(5):2275 1990. Unique Identifier : AIDSLINE ICDB/91669624
Margolin DH; Univ. of Pennsylvania

Abstract: Interleukin-2 is a T cell derived lymphokine which plays a central role in immune responses. This dissertation examines three issues relating to in vitro regulation and function of interleukin-2 receptors on normal human T lymphocytes and cells infected by the retrovirus HTLV-I. Influence of cyclosporin-A on interleukin-2 receptors. Cyclosporin-A suppressed proliferation of resting T cells following exposure to antigen or mitogen. Exogenous recombinant interleukin-2 failed to reconstitute proliferation by cyclosporin-A-treated peripheral blood mononuclear cells (PBMC). The ability of interleukin-2 to augment interleukin-2 receptor induction also was reduced by cyclosporin-A. Thus, cyclosporin-A appears to inhibit acquisition of interleukin-2 responsiveness. Using an 125I-interleukin-2 binding assay and Scatchard analysis, we found that cyclosporin-A inhibited the induction of both the alpha- and beta-chain of the interleukin-2 receptor. Thus, reduced interleukin-2 receptor expression contributes to cyclosporin-A immunosuppression. Production and immunoregulatory functions of soluble interleukin-2 receptor (Tac). We investigated the kinetics of soluble Tac production in vitro, and also identified an immunoregulatory role for soluble Tac. Purified recombinant soluble Tax (10-100 nM) inhibited a variety of leukocyte responses mediated by interleukin-2 receptor beta-chain, including the direct activation of resting PBMC by interleukin-2, induction of natural killer cell cytotoxicity and interferon-gamma production. Soluble Tac selectively inhibited interleukin-2-dependent responses, without demonstrable toxicity to an interleukin-2 independent cell line. Since soluble Tac, lacking only the cytoplasmic and transmembrane domains, did not bind to cells expressing interleukin-2 receptor-beta, these domains likely mediate interaction of Tac (interleukin-2 receptor-alpha) with interleukin-2 receptor-beta. We conclude that soluble Tac is an immunomodulator, and suggest that interleukin-2 binding by soluble Tac and interleukin-2 receptor-beta is competitive. These conclusions have implications for interleukin-2 receptor models. Activation of HTLV-I viral replication by interleukin-2. Interleukin-2 increased the accumulation of HTLV-I gag, pol, and env proteins as well as cellular interleukin-2R-alpha, whereas CD3 and HLA-DR proteins were unaffected by interleukin-2. Elevated reverse transcriptase activity in culture supernatants indicated that interleukin-2 also promotes the release of virions. Analysis of mRNA revealed that interleukin-2 acts at a pre-translational level in augmenting gene expression. We conclude that interleukin-2 may participate in the activation of retroviral genes following immunologic activation. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD90-26605)
Keywords: Cells, Cultured Cyclosporins/PHARMACOLOGY Gene Expression Regulation, Viral/DRUG EFFECTS Genes, Viral Human HTLV-I/*GENETICS/IMMUNOLOGY/PHYSIOLOGY Immunosuppression Interleukin-2/PHARMACOLOGY Receptors, Interleukin-2/DRUG EFFECTS/*GENETICS/IMMUNOLOGY Recombinant Proteins/PHARMACOLOGY T-Lymphocytes/IMMUNOLOGY/*MICROBIOLOGY Virus Replication/DRUG EFFECTS THESISKWDcells,culturedcyclosporins/pharmacologygeneexpressionregulation,viral/drugeffectsgenes,viralhumanhtlv-i/KWDgenetics/immunology/physiologyimmunosuppressioninterleukin-2/pharmacologyreceptors,interleukin-2/drugeffects/KWDgenetics/immunologyrecombinantproteins/pharmacologyt-lymphocytes/immunology/KWDmicrobiologyvirusreplication/drugeffectsthesis
910330
M9130604

Copyright © 1991 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1991. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1991. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .