ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids.

Abstract

Identification of the components of protective immunity are crucial for the development of effective prophylactic and therapeutic vaccine strategies. Analysis of HIV-specific responses in exposed but uninfected individuals might thus provide a unique resource to elucidate the components and correlates of protective immunity to HIV. In the present study we analyzed HIV-specific cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed to body fluids from HIV-positive individuals. HCW exposed to blood from HIV-negative individuals as well as healthy donors served as controls. Cytotoxic T lymphocyte (CTL) responses to HlIV envelope (env) peptides were detected in 7/20 (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers exposed to uninfected blood or the seven healthy blood donors studied. HIV-specific CTL responses were detected only after in vitro stimulation, and were MHC class I restricted. No MHC class I restriction elements were uniformly identified among the different responders. 21/28 (75%) HCW exposed to contaminated blood responded to env as measured by IL-2 production to the peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were seronegative on repeated ELISA tests, and no evidence of infection was obtained by PCR analysis. These findings indicate that a single exposure to HIV can induce CTL immunity to HIV antigens, in the absence of other evidence of infection. (J. Clin. Invest. 1995. 96:867-876.)

Lack of infection in HIV-exposed individuals is associated with a strong CD8+cell noncytotoxic anti-HIV response

“…The inhibition of virus replication measured in the CD8 ϩ cell assay described in this report is not the result of cellular cytotoxicity, an immune response that has been observed by others in EU populations (10)(11)(12)(13)). This conclusion is based on the following observations: (i) No HIV-specific CTLs were detected in cohort A; (ii) The CD8 ϩ effector cell inputs used in the suppression assay were below that typically required to detect cytotoxicity (i.e., 40:1); and (iii) No effort was made to match target and effector cells for MHC antigens.…”

“…The HIV resistance of a small fraction of EU subjects has been attributed to an inherited genetic mutation, specifically a 32-bp deletion (⌬32) resulting in lack of expression of the CCR5 molecule (6,7). Additionally, the presence of certain cellular immune responses, such as proliferation to HIV-derived peptides (8,9) or HIV-specific cytotoxic T-lymphocyte (CTL) activity (10)(11)(12)(13) have been reported in some of the EU subjects evaluated.…”

Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1.

“…A vigorous virus-specific CTL response is a major component of the host immune response in long-term nonprogressors (5)(6)(7). The observation that CTL activity declines with disease progression (7,8) and the demonstration of HIV-1-specific CTL activity in exposed uninfected individuals further supports a protective role for CTL (9,10). These data, together with similar data from animal models in which antiviral CTL can prevent disease (11) as well as clear established infections (12), suggest that HIV-1-specific CTL are likely to have a protective activity against HIV infection.…”

Perforin-low memory CD8+cells are the predominant T cells in normal humans that synthesize the β-chemokine macrophage inflammatory protein-1β

“…Those studies suggest that ␤-chemokines are synthesized by normal CD8 ϩ T cells that have a CTL effector phenotype. Thus, it is possible that ␤-chemokines contribute to the correlations between CTL and the reduction of viral loads (14)(15)(16)(17)(18) or protection against infection with HIV-1 (19)(20)(21)(22).…”