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Leukemia Inhibitory Factor, Oncostatin M, IL-6, and Stem Cell Factor mRNA Expression in Human Thymus Increases with Age and Is Associated with Thymic Atrophy¹

Gregory D. Sempowski^*,, Laura P. Hale, John S. Sundy^*, Janice M. Massey^*, Richard A. Koup^§, Daniel C. Douek^§, Dhavalkumar D. Patel^*, and Barton F. Haynes^2,*,

Departments of ^* Medicine, Immunology, and Pathology, Duke University Medical Center, Durham, NC 27710; and ^§ Department of Medicine, University of Texas Southwestern School of Medicine, Dallas, TX 75235

The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) and 34 myasthenia gravis thymuses (aged 4 to 75 years) during aging, and correlated cytokine mRNA levels with thymic signal joint (sj) TCR excision circle (TREC) levels, a molecular marker for active thymopoiesis. LIF, oncostatin M (OSM), IL-6, M-CSF, and stem cell factor (SCF) mRNA were elevated in normal and myasthenia gravis-aged thymuses, and correlated with decreased levels of thymopoiesis, as determined by either decreased keratin-positive thymic epithelial space or decreased thymic sjTRECs. IL-7 is a key cytokine required during the early stages of thymocyte development. Interestingly, IL-7 mRNA expression did not fall with aging in either normal or myasthenia gravis thymuses. In vivo administration of LIF, OSM, IL-6, or SCF, but not M-CSF, i.p. to mice over 3 days induced thymic atrophy with loss of CD4⁺, CD8⁺ cortical thymocytes. Taken together, these data suggest a role for thymic cytokines in the process of thymic atrophy.