| First Author | Chrobak P | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 7 | Pages | 3948-59 |
| PubMed ID | 20826747 | Mgi Jnum | J:164287 |
| Mgi Id | MGI:4831058 | Doi | 10.4049/jimmunol.1001064 |
| Citation | Chrobak P, et al. (2010) HIV-1 Nef disrupts maturation of CD4+ T cells through CD4/Lck modulation. J Immunol 185(7):3948-59 |
| abstractText | The HIV-1 Nef protein is a major determinant of HIV-1 pathogenicity. It has been found to induce thymocyte depletion, but the mechanisms involved are not completely understood. Also, nothing is known about its effects on thymocyte selection. We used the CD4C/HIV(Nef) transgenic (Tg) mice, which develop a profound CD4(+) T cell lymphopenia, to study their thymic development. We report that HIV-1 Nef causes depletion of double-positive thymocytes and impairs selection and lineage commitment of CD4(+) single-positive thymocytes. This latter defect could be relieved by increasing the affinity of the TCR-MHC interaction or by allowing CD4(+) T cell maturation to proceed in absence of the CD4 tail, in double-Tg (Nef x CD4(tailless)) mice or in the presence of constitutively active Tg Lck(Y505F). These rescue strategies also resulted in reversal of peripheral CD4(+) T cell lymphopenia. Our data indicate that impairment of Lck-mediated CD4 coreceptor signaling by Nef is an important in vivo mechanism of HIV-1 pathogenesis. |
