Characterization of HIV-1-specific cytotoxic T lymphocytes expressing the mucosal lymphocyte integrin CD103 in rectal and duodenal lymphoid tissue of HIV-1-infected subjects.
Acute HIV-1 infection depletes CD4(+) T cells in gut-associated lymphoid tissue (GALT). The failure of containment of local viral replication, and consequent CD4(+) T cell depletion, might be due to delayed mobilization of effector CD8(+) T cells or absence of functioning HIV-1-specific CD8(+) T cell effectors within GALT. No studies have addressed human intestinal HIV-1-specific CD8(+) T cell functions. We sought to determine whether functional HIV-1-specific CTL were present in GALT and whether the repertoire differed from HIV-1-specific CTL isolated from peripheral blood mononuclear cells. From three HIV-1-infected subjects, we isolated HIV-1-specific CD8(+) T cells expressing the mucosal lymphocyte integrin CD103 from GALT. These antigen-specific effector cells could be expanded in vitro and lysed target cells in an MHC class I-restricted manner. HIV-1-specific CTL could be isolated from both duodenal and rectal GALT sites, indicating that CD8(+) effectors were widespread through GALT tissue. The breadth and antigenic specificities of GALT CTL appeared to differ from those in peripheral blood in some cases. In summary, we found HIV-1-specific CD8(+) effector T cells in GALT, despite HIV-1-induced CD4(+) T cell lymphopenia. This suggests that HIV-1-specific CTL in gut tissue can be maintained with limited CD4(+) T cell help.
Shacklett
B L
BL
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. bshackle#adarc.org
Beadle
T J
TJ
Pacheco
P A
PA
Grendell
J H
JH
Haslett
P A
PA
King
A S
AS
Ogg
G S
GS
Basuk
P M
PM
Nixon
D F
DF
D000328:Adult; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004386:Duodenum / Q000276:immunology / Q000821:virology; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D039001:Integrin alpha Chains; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000276:immunology / Q000821:virology
D015703:Antigens, CD; D015488:HIV Antigens; D039001:Integrin alpha Chains; C091367:alpha E integrins