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Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8⁺ Cytotoxic T Lymphocytes

L. Musey,^1, Y. Ding,¹ J. Cao,¹ J. Lee,¹ C. Galloway,¹ A. Yuen,² K. R. Jerome,^2,3 and M. J. McElrath^1,2,3*

Departments of Medicine,¹ Laboratory Medicine, University of Washington,³ Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109²

Received 26 June 2002/ Accepted 16 September 2002

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 TCRß 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.

Present address: Merck Research Laboratories, Blue Bell, PA 19422.