Enhancing of anti-viral activity against HIV-1 by stimulation of CD8+ T cells with thymic peptides.
HIV-1 can be neutralized by soluble factors produced and secreted by activated CD8+ T cells. Production of such anti-viral CD8 factors (including chemokines) can be induced with IL-2 or phytohaemagglutinin (PHA). In addition to PHA or IL-2, we have co-stimulated CD8+ T cells with PHA/IL-2 and a mixture of thymic peptides (TP) of molecular weights below 10 kD. For the activation, CD8+ T cells were purified from peripheral blood mononuclear cells of HIV-1- individuals and any resultant anti-viral activity was monitored using an HIV-1 neutralization assay. Using HIV-1 isolates highly resistant to chemokine inhibition we detected significantly higher levels of HIV-1 neutralizing activity in CD8+ T cell culture supernatants which had been co-activated with TP. When the TP-induced anti-viral activity was monitored, neutralization of both non-syncytia-inducing (NSI) and syncytia-inducing (SI) patient isolates was enhanced by 38% (NSI, PHA +/- TP), 66% (SI, PHA +/- TP), 28% (NSI, IL-2 +/- TP), and 57% (SI, IL-2 +/- TP) compared with the anti-viral activity present in supernatants from CD8+ T cell cultures stimulated only with PHA or IL-2. Peptide sequence analysis of purified TP showed that the TP mixture predominantly contains peptides with homology to human histone and collagen sequences. Our data demonstrate that CD8+ T cells are additionally activated by a mixture of TP. In this way, the production of HIV-1 neutralizing CD8 factors can be enhanced.
Müller
H
H
Bernhard Nocht Institute for Tropical Medicine, Department of Virology, Hamburg, Germany.
Mayer
G
G
Behnke
B
B
Heimüller
E
E
Hamscher
G
G
Immler
D
D
Siethoff
C
C
Meyer
H E
HE
Schreiber
M
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned; D015726:Giant Cells; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006657:Histones / Q000737:chemistry; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000627:therapeutic use*; D010835:Phytohemagglutinins / Q000494:pharmacology; D016415:Sequence Alignment; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013950:Thymus Gland / Q000737:chemistry*; D014020:Tissue Extracts / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D006657:Histones; D007376:Interleukin-2; D010455:Peptides; D010835:Phytohemagglutinins; D014020:Tissue Extracts; D003094:Collagen