Low-Level CD4(+) T Cell Activation in HIV

Low-Level CD4(+) T Cell Activation in HIV-Exposed Seronegative Subjects: Influence of Gender and Condom Use.

Immune activation has been suggested to increase susceptibility to human immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it could be deemed essential for mounting an effective antiviral immune response. In this study, Camara and colleagues compared levels of T cell activation between exposed seronegative partners in HIV-1 discordant couples and HIV-unexposed control subjects in Dakar, Senegal. Exposed seronegative subjects showed lower levels of CD38 expression on CD4(+) T cells than did control subjects. However, this was found to be associated with concurrent differences in the use of condoms: exposed seronegative subjects reported a higher degree of condom use than did control subjects, which correlated inversely with CD38 expression. In addition, they observed markedly higher levels of T cell activation in women compared with men, irrespective of sexual behaviour. These findings question the relevance of low-level CD4(+) T cell activation in resistance to HIV-1 infection and underscore the need to take gender and sexual behaviour characteristics of high-risk populations into account when analyzing correlates of protective immunity

Basic scientists have found that host factors such as genetic predisposition (e.g. CCR5-delta 32 mutation), intrinsic cellular defences (e.g. β-chemokines), and innate or adaptive immune responses (e.g. natural killer cell activity) may help explain why HIV-seronegative people resist HIV infection when they are exposed sexually multiple times. It is true that viral load in the partner is important, as are the characteristics of the infecting virus, however the low levels of immune activation found in a number of studies of exposed, seronegative people have been intriguing. It may mean fewer activated T cells are around for HIV to invade. However, this study suggests that basic scientists should be paying more attention to human behaviour and to sex. HIV-negative partners in Senegalese serodiscordant couples that always used condoms had decreased CD4+ T- cell activation compared to HIV-negative low risk controls. This was likely due to less exposure to genital secretions that can cause immune activation. This finding was independent of infection with herpes simplex virus-2 and was more marked in men (85% of male versus 46% of female seronegative partners reported always using condoms). More than condom use may be playing a role too since women generally seem to have higher T-cell activation. In studies of seronegative exposed individuals aimed at finding promising avenues for therapeutics and vaccine development, it is important to know about the people behind the samples: their sex and their condom use practices.