T cell activation and proliferation characteristic for HIV-Nef transgenic mice is lymphopenia induced.
The HIV-Nef protein has been implicated in generating high viral loads and T cell activation. Transgenic (tg) mice with constitutive T cell-specific Nef expression show a dramatic reduction in T cell number and highly increased T cell turnover. Previous studies in Nef tg mice attributed this T cell activation to a direct effect of Nef at the cellular level. Given the strongly reduced peripheral T cell numbers, we examined whether this enhanced T cell division might instead be lymphopenia induced. Adoptively transferred naive wild-type T cells into lymphopenic Nef tg mice showed high T cell turnover and obtained the same effector/memory phenotype as the autologous Nef tg T cells, supporting the idea that the microenvironment determines the phenotype of the T cells present. Moreover, in bone marrow chimeras from mixtures of wild-type and Nef tg bone marrow, with a full T cell compartment containing a small proportion of Nef tg T cells, Nef tg T cells kept a naive phenotype. These results demonstrate that T cell activation in the Nef tg mice is lymphopenia induced rather than due to a direct T cell-activating effect of Nef.
Koenen
Paul G F
PG
Department of Immunology, University Medical Center, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Hofhuis
Frans M
FM
Oosterwegel
Mariëtte A
MA
Tesselaar
Kiki
K
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D049109:Cell Proliferation; D002678:Chimera / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D006678:HIV / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus