Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent

• Published in: AIDS (London) Vol. 7; no. 6; p. 807
• Main Authors: Bell, S J, Geczy, A F, Russell-Jones, G J, Croft, S, Cooper, D A, Penny, R
• Format: Journal Article
• Language: English
• Published: England 01.06.1993
• Subjects: Adjuvants, Immunologic - pharmacology; Amino Acid Sequence; Antigens, Bacterial - immunology; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - pharmacology; Cells, Cultured; Escherichia coli; Escherichia coli Proteins; Haplotypes - genetics; HIV - immunology; HIV Envelope Protein gp41 - immunology; HIV Infections - blood; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Immunodominant Epitopes - immunology; Immunologic Memory; Interleukin-2 - pharmacology; Molecular Sequence Data; Peptide Fragments - immunology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199306000-00008

To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.