Immune Aging

The adaptive and innate immune systems undergo dramatic changes with age, globally designated as immunosenescence. The frequencies and proliferative potentials of hematopoietic stem cells decline during adulthood and bottom out during the last third of life. The thymus involutes, and production of new T cells essentially ceases between the ages of 40-50 years. Age-related incompetence of the immune system becomes clinically relevant after the age of 50, when incidences of cancer rise, reactivation rates of chronic viral infections increase, and new infections are associated with greater morbidity and mortality. Also, cellular senescence of the immune system emerges as a critical factor in autoimmune disease (e.g., giant cell arteritis and rheumatoid arthritis) and affects the progression and complications of degenerative diseases, particularly atherosclerosis. Researchers in the Lowance Center identify age-dependent changes in the immune system, examine their functional relevance, and develop therapeutic strategies to delay aging and restore immune function.

Publications

Goronzy JJ , Lee W-W, Weyand CM. Aging and T-cell diversity. Exp Gerontol In press.

Diaz-Borjon A, Weyand CM, Goronzy JJ. Treatment of chronic inflammatory diseases with biologic agents: Opportunities and risks for the elderly. Exp Gerontol 41:1250-1255, 2006.

Goronzy JJ , Fujii H, Weyand CM. Telomeres, immune aging and autoimmunity. Exp Gerontol 41:246- 251, 2006 .

Henel G, Singh K, Cui D, Pryshchep S, Lee W, Weyand CM, Goronzy JJ. Uncoupling of T cell effector functions by inhibitory killer immunoglobulin-like receptors. Blood 107:4449-4457, 2006 .

Goronzy JJ, Weyand CM. T-cell development and receptor diversity during aging. Curr Opin Immunol 17:468-475, 2005.

Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ . The influence of age on T cell generation and TCR diversity. J Immunol 174:7446-7452, 2005.

Xu J, Vallejo AN, Jiang Y, Weyand CM, Goronzy JJ. Distinct transcriptional control of killer immunoglobulin-like receptors in natural killer (NK) and in T cells. J Biol Chem 280:24277-24285, 2005.

Snyder MR, Weyand CM, Goronzy JJ. The double life of NK receptors: Stimulation or costimulation. Trends in Immunol 25:25-32, 2004.

Snyder MR, Nakajima T, Leibson PJ, Weyand CM, Goronzy JJ. Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. J Immunol 173:3725-3731, 2004.

Vallejo AN, Weyand CM, Goronzy JJ. T-cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection. Trends Mol Med 10:119-124, 2004.

Weyand CM, Goronzy JJ. Stem cell aging and autoimmunity in rheumatoid arthritis. Trends Mol Med 10:426-433, 2004.

Goronzy JJ, Weyand CM. Ageing, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity - catalysts of autoimmunity and chronic inflammation. Arthritis Res Ther 5:225-234, 2003.

Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 38:833-841, 2003.

Snyder MR, Lucas M, Vivier E, Weyand CM, Goronzy JJ. Selective activation of the c-Jun NH 2- terminal protein kinase signaling pathway by stimulatory KIR in the absence of KARAP/DAP12 in CD4 + T cells. J Exp Med 197:437-449, 2003.

Warrington KJ, Vallejo AN, Weyand CM, Goronzy JJ. CD28 loss in senescent CD4 + T Cells: Reversal by interleukin-12 stimulation. Blood 101:3543-3549, 2003.

Snyder MR, Muegge L-O, Offord C, O’Fallon WM, Bajzer Z, Weyand CM, Goronzy JJ. Formation of the killer immunoglobulin-like receptor repertoire on CD4 +CD28 null T cells. J Immunol 168:3839-3846, 2002.

Vallejo AN, Bryl E, Klarskov K, Naylor S, Weyand CM, Goronzy JJ. Molecular basis for the loss of CD28 expression in senescent T cells. J Biol Chem 277:46940-46949, 2002.

Weyand CM, Goronzy JJ. Premature immunosenescence in rheumatoid arthritis. J Rheumatol 29:1141- 1146, 2002.

Vallejo AN, Weyand CM, Goronzy JJ. Functional disruption of the CD28 gene transcriptional initiator in senescent T cells. J Biol Chem 276:2565-2570, 2001.

Bryl E, Vallejo AN, Weyand CM, Goronzy JJ. Down-regulation of CD28 expression by TNF-α Immunol 167:3231-3238, 2001.

Goronzy JJ, Fulbright JW, Crowson CS, Poland GA, O’Fallon WM, Weyand CM. Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. J Virol 75:12182-12187, 2001.

Vallejo AN, Schirmer M, Weyand CM, Goronzy JJ. Clonality and longevity of CD4+CD28null T cells is associated with defects in apoptotic pathways. J Immunol 165:6301-6307, 2000.

Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ. Modulation of CD28 expression: Distinct regulatory pathways during activation and replicative senescence. J Immunol 162:6572-6579, 1999.

Vallejo A, Nestel AR, Schirmer M, Weyand CM, Goronzy JJ. Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene specific nuclear factor binding activity. J Biol Chem 273:8119-8129, 1998.

Weyand CM, Brandes JC, Schmid t D, Fulbright JW, Goronzy JJ. Functional properties of CD4+CD28- T cells in the aging immune system. Mech Ageing Develop 102:131-147, 1998.