Clinical (Viro-) Immunology
T cell dynamics in Mice@
Kiki Tesselaar
T cells are important players in the adaptive immunity to (viral) pathogens. Loss of naïve T cells leads to increased susceptibility to infections as seen in HIV infected patients but also in the elderly. T cell production by the thymus and average lifespan of the peripheral T cells determine steady state T cell numbers. We are interested in the contribution of these factors under different (pathological) situations like aging, chronic immune activation and immune reconstitution.
To overcome the limitations involved in measurement and manipulation of the T-cell compartment in men, we use mouse models to determine the contribution of these factors to T-cell homeostasis. Currently we are performing thymectomy in combination with heavy water labeling to test the relative contribution of thymus output and peripheral T-cell turnover. The effects of immune hyper-activation on the dynamics of the T-cell compartment are tested in different model systems, varying from CD70-transgenic mice, OVA-TCR transgenic mice and Poly-[IC] treatment. We are investigating whether there are intrinsic differences between CD4 and CD8 T cells in response to immune hyper-activation, or during reconstitution after T-cell depletion with monoclonal antibodies.
In a joint project with M. Oosterwegel, the consequences of transgenic expression of the HIV-derived protein NEF on T-cell homeostasis are being investigated. Future plans include detailed analyses of T-cell dynamics in healthy aging mice with an emphasis on the pool of recent thymus emigrants.
Members- Sigrid Otto, technician
- Ellen Veel, PhD student
- Vera van Hoeven, PhD student
- Steven van Lelyveld, PhD student
Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool.Vrisekoop N, den Braber I, de Boer AB, Ruiter AF, Ackermans MT, van der Crabben SN, Schrijver EH, Spierenburg G, Sauerwein HP, Hazenberg MD, de Boer RJ, Miedema F, Borghans JA, Tesselaar K.
Proc Natl Acad Sci U S A. 2008 Apr 22;105(16): 6115-20
ICOS contributes to T cell expansion in CTLA-4 deficient mice.van Berkel ME, Schrijver EH, Hofhuis FM, Sharpe AH, Coyle AJ, Broeren CP, Tesselaar K, Oosterwegel MA.
J Immunol. 2005 Jul 1;175(1):182-8
Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals progressing to AIDS with CMV end-organ disease.
Bronke C, Palmer NM, Jansen CA, Westerlaken GH, Polstra AM, Reiss P, Bakker M, Miedema F, Tesselaar K, van Baarle D.
J Infect Dis. 2005 Mar 15;191(6):873-80
Expression of the murine CD27 ligand CD70 in vitro and in vivo.Tesselaar K, Xiao Y, Arens R, Schijndel GM, Schuurhuis DH, Mebius RE, Borst J, van Lier RA.
J Immunol. 2003 Jan 1;170(1):33-40
Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions.Tesselaar K, Arens R, van Schijndel GM, Baars PA, van der Valk MA, Borst J, van Oers MH, van Lier RA.
Nat Immunol. 2003 Jan;4(1):49-54
Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion.
Arens R, Tesselaar K, Baars PA, van Schijndel GM, Hendriks J, Pals ST, Krimpenfort P, Borst J, van Oers MH, van Lier RA.
Immunity. 2001 Nov;15(5):801-12
2003-2007
LSBR
Mechanisms of CD4 T cell depletion: A study of T cell dynamics in CD70 and Nef transgenic (TG) mice.
Dr. K. Tesselaar.
2005-2009
NWO Vici; Prof.dr R.de Boer
Population Dynamics of T Lymphocytes.
Prof. R. de Boer & Dr. K. Tesselaar.