An estimated 5–10 million people worldwide are now infected with HIV-1 and related retroviruses [1]. Despite the detection of both humoral and cellular immune re-sponses in infected people, the exact role of the immune system in the pathogenesis of HIV-1 infection remains unclear. A number of lines of evidence, however, suggest that HIV-1-specific immune responses may serve a protective role. Foremost among these is the demonstration that the majority of adults remain asymptomatic for years after infection, despite the presence of persistent viremia [2]. This is in marked contrast to immunologically im-mature infants infected by perinatal transmission, who usually develop pathologic consequences of HIV-1 infec-tion within 24 months|| 3]. A growing body of evidence now suggests that HIV-1-specific cytotoxic Thmphocytes (CTL) may be a particularly important component of the host defense against this virus|| 4–6]. CTL have been demonstrated to be one of the early host defenses generated in response to a variety of viral infections [7]. These cells eliminate virus-infected cells by recognizing viral protein fragments on the infected cell surface. This recognition is mediated through the T-cell receptor (TCR) of the CTL, which is thought to interact with a binary complex of a processed viral oligopeptide fragment and a human leukocyte antigen (HLA) molecule on the surface of the target cell [8]. CTL recognition can then lead to lysis of the infected cells. Evidence from numerous viral systems indicates that virus-specific CTL serve a protective role [9–14]. For example, in murine infections with influenza A virus, virus-specific CTL are generated before the production of significant levels of antibody, and adoptive transfer of these cells to histocompatible mice challenged subsequently with influenza A results in decreased viral titers and decreased mortal-ity [9]. Virus-specific CTL are also generated in response to murine leukemia retroviruses (MuLV), and have been shown to mediate rejection of MuLV-induced tumors [10–12]. In humans, virus-specific CTL contribute to re-covery from both cytomegalovirus (CMV) and influenza A virus infections [13, 14].

The hallmark of HIV-1 infection is the development of profound immunosuppression, and yet vigorous HIV-1-specific CTL responses have been detected in infected people [4, 5]. These responses subsequently diminish with progression of disease [61516]. In this review, we consider the nature of the cytotoxic effector cells mediating these responses, the viral antigens recognized, the role of HLA antigens, and the potential participation of CTL in HIV-1 pathogenesis and protective immunity.