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T Cell Activation and Proliferation Characteristic for HIV-Nef Transgenic Mice Is Lymphopenia Induced¹

Department of Immunology, University Medical Center, Utrecht, The Netherlands

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by Grant Number 6011 from Aids Fonds Netherlands.

² Address correspondence and reprint requests to Dr. Kiki Tesselaar, Department of Immunology, University Medical Center, Lundlaan 6, Room KC02.085.2, 3584 EA Utrecht, The Netherlands. E-mail address: k.tesselaar{at}umcutrecht.nl

³ Abbreviations used in this paper: tg, transgenic; wt, wild type; PLN, peripheral lymph node; MFI, mean fluorescence intensity; E/M, effector/memory.