Comparison of HIV-specific CD8 T-cell responses among uninfected individuals exposed to HIV parenterally and mucosally.
OBJECTIVE
To assess the influence of route of HIV exposure on the development of HIV-specific CD8 T-cell responses in exposed, uninfected (EU) individuals.


METHODS
Two groups of EU exposed to virus through either sexual or intravenous contact were studied. Group I included subjects (n = 20) who had unprotected sexual contact with known HIV-infected partners and no intravenous HIV exposure; Group II included individuals (n = 27) who had shared needles with HIV-infected partners and had no sexual exposure to this virus. Between-group comparisons were made for the proportion of responders, breadth, magnitude, and specificity of HIV-specific responses.


METHODS
: The interferon-gamma ELISPOT assay was used to detect HIV-specific effector activity. Peripheral blood mononuclear cells (PBMC) from each subject were stimulated with a panel of HIV peptides restricted to the MHC class I alleles expressed by the individual.


RESULTS
A similar proportion of EU tested from each group (35.0% Group I versus 22.2% Group II) recognized at least one HIV peptide. Group I and II subjects recognized HIV peptides with a similar cumulative intensity of 130 +/- 67.5 and 182.9 +/- 184.2 spot forming cells/1 x 10 PBMC, respectively, and similar magnitude per stimulatory peptide of 82.7 and 78.4 SFC/1 x 10 PBMC, respectively. The proportion of stimulatory peptides derived from HIV Gag, reverse transcriptase, Env, and Nef was not significantly different between the two EU groups. HLA-A*0201 restricted HIV epitopes immunodominant in infected individuals are rarely stimulatory in EU subjects.


CONCLUSIONS
Both mucosal and parenteral exposure to HIV can elicit HIV-specific CD8 T-cell responses with similar characteristics.
Makedonas
George
G
The Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Canada.
Bruneau
Julie
J
Alary
Michel
M
Tsoukas
Christos M
CM
Lowndes
Catherine M
CM
Lamothe
François
F
Bernard
Nicole F
NF
D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016485:Needle Sharing / Q000009:adverse effects; D015229:Sexually Transmitted Diseases, Viral / Q000276:immunology; D015819:Substance Abuse, Intravenous / Q000150:complications; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D014764:Viral Proteins; D007371:Interferon-gamma