Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.
OBJECTIVE
To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity.


METHODS
CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Bell
S J
SJ
Centre for Immunology, St Vincent's Hospital, Sydney, New South Wales, Australia.
Geczy
A F
AF
Russell-Jones
G J
GJ
Croft
S
S
Cooper
D A
DA
Penny
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006678:HIV / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000097:blood; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D015700:HIV Envelope Protein gp41; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D010446:Peptide Fragments; C036297:TraT protein, E coli