Recently, by comparing the capture of a whole range of molecules associated to the plasma membrane, we found that CD4 was actually among the molecules that were most efficiently captured by murine T and B cells (manuscript submitted). one finds the antigen itself but also additional molecules including costimulatory molecules, adhesion molecules, and various receptors [2] which can confer novel functions to acceptor lymphocytes. For instance, in the case of CD8+ CTL, capture of the antigen has been shown to result in their killing by CTL sharing the same antigen-specificity, a phenomenon known as fratricide and thought to be important for the contraction of the CTL response [3]. Another kind of consequence is that bystander captured molecules could help pathogens to spread through the organism. Natural killer cells (NK cells), which also perform trogocytosis, have recently been shown to capture virus receptors such as CD21, the receptor for Epstein-Barr virus (EBV) [4] and CD155, the receptor for poliovirus [5]. Whether these receptors are fully functional after their capture by NK cells remains unknown, but at least in the case of the EBV receptors, we have shown that its capture by NK cells confers them the ability to bind EBV [4]. The human CD4 antigen, the Human Immunodeficiency Virus (HIV) receptor, has previously been shown to be captured by Erythromycin estolate CD8+ T cells in a rat [6] and in a mouse [7] model. Recently, by comparing the capture of a whole range of molecules associated to the plasma membrane, we found that CD4 was actually among the molecules that were most efficiently captured by murine T and B cells (manuscript submitted). Since trogocytosis had recently been implicated in HIV propagation between CD4+ T cells [8], we hypothesized that it could Erythromycin estolate also play a role in the virus spreading to CD8+ T cells. Indeed, CD8+ CTL play an important role in the immune response against HIV infection [9], since, until the virus escapes the immune response, they are initially responsible for the elimination of most CD4+ infected cells until the virus escapes the immune response. Incidentally, it has been shown that during the late stages of HIV infection, a minute fraction of CD8+ T cells becomes infected [10] although the mechanism(s) leading to infection is(are) unknown [11, 12]. Among the possible mechanisms leading to CTL infection, it has been proposed that HIV could infect those CTL that express CD4 during their activation [13C20]. A recent report also suggests that CD8+CD4dim cells are enriched in anti-HIV lymphocytes [21]. It should be noted, however, that CD4 expression is not classically associated with the activation of CD8+ T cells and that not all HIV-infected CD8+ T cells are CD4+, suggesting that additional mechanisms may be involved. It has also been argued that double-positive CD4+CD8+ thymocytes, which could end up Mouse monoclonal to Human Serum Albumin as CD8+ T cells at the end of their differentiation, could be targeted by HIV [22]. This hypothesis does, however, seem unlikely as a general explanation for the occurrence of HIV-infected CD8+ T cells because most of those are usually not na?ve cells. Finally, some Erythromycin estolate HIV strains have been shown to use CD8 as a receptor [23] but these particular virions were only isolated after many steps of enrichment, suggesting their very low frequency in natural viral stocks. Of interest, De Maria et al. reported that CD8+ T cells could be infected in culture, provided that CD4+ T cells were present, suggesting that direct contact between the two cells types is important for CTL infection [24, 25]. Combined with the notion that trogocytosis requires cell-to-cell contacts [2, 26], this last observation suggests that it is worth investigating if CD8+ T cells could capture CD4 from CD4-expressing cells in a coculture and, if so, whether this mechanism could result in CD8+ T cell infection. 2. Materials and Methods 2.1. Cell Lines and Mice The T2 human lymphoblastoid cell line, which expresses HLA-A2.1 naturally, was used as a target cell in antigen (Ag)-mediated trogocytosis experiments. Erythromycin estolate The mouse mastocytoma cell line P815, which naturally expresses Fcwere performed as previously described [27]. Target cells were cell surface biotinylated or not and incubated with effector CD8+ T cells (E : T = 1.