Ontogeny and specificities of mucosal and blood human immunodeficiency virus type 1-specific CD8(+) cytotoxic T lymphocytes.
Induction of adaptive immunity to human immunodeficiency virus type 1 (HIV-1) at the mucosal site of transmission is poorly understood but crucial in devising strategies to control and prevent infection. To gain further understanding of HIV-1-specific T-cell mucosal immunity, we established HIV-1-specific CD8(+) cytotoxic T-lymphocyte (CTL) cell lines and clones from the blood, cervix, rectum, and semen of 12 HIV-1-infected individuals and compared their specificities, cytolytic function, and T-cell receptor (TCR) clonotypes. Blood and mucosal CD8(+) CTL had common HIV-1 epitope specificities and major histocompatibility complex restriction patterns. Moreover, both systemic and mucosal CTL lysed targets with similar efficiency, primarily through the perforin-dependent pathway in in vitro studies. Sequence analysis of the TCRbeta VDJ region revealed in some cases identical HIV-1-specific CTL clones in different compartments in the same HIV-1-infected individual. These results clearly establish that a subset of blood and mucosal HIV-1-specific CTL can have a common origin and can traffic between anatomically distinct compartments. Thus, these effectors can provide immune surveillance at the mucosa, where rapid responses are needed to contain HIV-1 infection.
Musey
L
L
Departments of Medicine, University of Washington, Seattle 98109, USA.
Ding
Y
Y
Cao
J
J
Lee
J
J
Galloway
C
C
Yuen
A
A
Jerome
K R
KR
McElrath
M J
MJ
D002584:Cervix Uteri / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D008297:Male; D012007:Rectum / Q000276:immunology; D012661:Semen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag