Parallel human immunodeficiency virus type 1-specific CD8+ T-lymphocyte responses in blood and mucosa during chronic infection.
Gut-associated lymphoid tissue is the major reservoir of lymphocytes and human immunodeficiency virus type 1 (HIV-1) replication in vivo, yet little is known about HIV-1-specific CD8+ T-lymphocyte (CTL) responses in this compartment. Here we assessed the breadth and magnitude of HIV-1-specific CTL in the peripheral blood and sigmoid colon mucosa of infected subjects not on antiretroviral therapy by enzyme-linked immunospot analysis with 53 peptide pools spanning all viral proteins. Comparisons of blood and mucosal CTL revealed that the magnitude of pool-specific responses is correlated within each individual (mean r2 = 0.82 +/- 0.04) and across all individuals (r2 = 0.75; P < 0.001). Overall, 85.1% of screened peptide pools yielded concordant negative or positive results between compartments. CTL targeting was also closely related between blood and mucosa, with Nef being the most highly targeted (mean of 2.4 spot-forming cells [SFC[/10(6) CD8+ T lymphocytes/amino acid [SFC/CD8/aa]), followed by Gag (1.5 SFC/CD8/aa). Finally, comparisons of peptide pool responses seen in both blood and mucosa (concordant positives) versus those seen only in one but not the other (discordant positives) showed that most discordant results were likely an artifact of responses being near the limit of detection. Overall, these results indicate that HIV-1-specific CTL responses in the blood mirror those seen in the mucosal compartment in natural chronic infection. For protective or immunotherapeutic vaccination, it will be important to determine whether immunity is elicited in the mucosa, which is a key site of initial infection and subsequent HIV-1 replication in vivo.
Ibarrondo
F Javier
FJ
UCLA AIDS Institute, Department of Medicine, Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA.
Anton
Peter A
PA
Fuerst
Marie
M
Ng
Hwee L
HL
Wong
Johnson T
JT
Matud
Jose
J
Elliott
Julie
J
Shih
Roger
R
Hausner
Mary Ann
MA
Price
Charles
C
Hultin
Lance E
LE
Hultin
Patricia M
PM
Jamieson
Beth D
BD
Yang
Otto O
OO
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D012809:Colon, Sigmoid / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015693:Gene Products, nef; D015488:HIV Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus