Cell-Mediated Immune Response to Human Immunodeficiency Virus (HIV) Type 1 in Seronegative Homosexual Men with Recent Sexual Exposure to HIV-1

Abstract

Although human immunodeficiency virus (HIV) type 1 infection is efficiently transmitted by sexual intercourse, some individuals whose sexual behavior places them at extremely high risk for infection have nevertheless remained HIV-1-seronegative. An investigation was undertaken to determine whether such individuals have circulating T helper cells that are sensitized to HIV-1. Five very high risk men who had recent sexual exposure to HIV-1 were studied. Peripheral blood mononuclear cells from all 5 produced interleukin (IL)-2 in culture in response to synthetic amphipathic HIV-1 envelope peptides. One of the 5 high-risk men has subsequently seroconverted, while 4 have remained seronegative. All were initially culture-negative, and those who have remained seronegative were also virus-negative by polymerase chain reaction (PCR) testing 10 months after they were first studied. These results demonstrate that a cell-mediated immune response to HIV-1 can be detected in the absence of a humoral immune response in individuals recently exposed to HIV-1. Furthermore, IL-2 production by T cells in response to synthetic peptides may be a more sensitive test for exposure to HIV-1 than antibody, lymphoproliferation, or PCR tests.

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau

“…showed a significant inverse correlation between the level of CTL activity and proviral DNA load, indicating a role for CTL in the control of the HIV-2 infection [44]. The finding of viral-specific cell-mediated immune responses, as measured by T cellproliferation in HIV-2 EU individuals, is consistent with studies of HIV-1 EU individuals, including homosexual men [5], children born to HIV-1-infected women [6], HIV-1 discordant couples [7] and highly exposed sex workers [8,[12][13][14][15][16][17], demonstrating HIV-1-specific T helper cell responses and/or CTL in a proportion of these individuals. The observations in the present study provide further indications for a role of cell-mediated immune responses in the control of HIV-2 infection and are in line with the view of HIV-2 infection resembling the cases with a less progressive HIV-1 infection, often termed long-term non-progressors.…”

“…Evidence has been provided for HIV-1-specific immune responses associated with protection against HIV-1 infection. As in other viral infections [3,4], cell-mediated immunity (CMI) appears to play a crucial role; HIV-1-specific cytotoxic T lymphocytes (CTL) as well as lymphoproliferative responses have been demonstrated in several groups of HIV-1-exposed uninfected (EU) individuals and in HIV-1-infected long-term non-progressors (LTNP) [4][5][6][7][8][9][10][11][12][13][14][15][16]. This includes the wellcharacterized group of HIV-exposed persistently seronegative (HEPS) commercial sex workers (CSW) in Nairobi, Kenya [13][14][15][16][17].…”

Diversity and virulence thresholds in AIDS

“…The virus grows exponentially and declines as a function of the immune reaction. The latter is supposedly due to specific antibodies and/or to cytotoxic T cells (3,21,23,24). For simplicity, we here assume that the immune reaction is proportional to the concentration of HIV-specific CD4+ helper T cells.…”

A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection

“…The notion that a subset of human subjects remains uninfected despite multiple exposures to HIV-1 has been known for years (8,9). Natural resistance to HIV-1 *Scientific Institute for Recovery and Care E. Medea, 23842 Bosisio Parini, Italy; is thought to result from a favorable genetic and immunologic milieu that generates systemic and mucosal cell-mediated immune responses (10)(11)(12)(13).…”