Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide.
Lenalidomide, an analog of thalidomide, modified responses of stimulated T cells from healthy young (ages 21-40 years) and old (≥ age 65 years) subjects. At 0.03 μM to 1 μM, lenalidomide enhanced generation of IL-2 and IFN-γ by T cell receptor-stimulated T cells of young subjects up to respective maximum increases of 17-fold and three-fold, but at 0.3 μM and 1 μM suppressed IL-17 generation. The same concentrations of lenalidomide enhanced IL-2 and IFN-γ generation by stimulated T cells of old subjects more, with greater respective maximal increases of up to 120-fold and six-fold, without suppressing IL-17 generation. Lenalidomide enhanced proliferation and suppressed apoptosis of stimulated T cells from old subjects, by IL-2-dependent mechanisms, and restored diminished T cell chemotactic responses to CCL21 and sphingosine 1-phosphate. The reversal of T cell abnormalities of immunosenescence by low concentrations of lenalidomide suggest a potential for improvement of immunity in the elderly.
Department of Medicine, University of California, San Francisco, CA, USA.
Mei-Chuan
MC
Huang
Nigel H
NH
Greig
Weiming
W
Luo
David
D
Tweedie
Janice B
JB
Schwartz
Dan L
DL
Longo
Luigi
L
Ferrucci
William B
WB
Ershler
Edward J
EJ
Goetzl
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult; D051020:bcl-X Protein / Q000276:immunology
C515478:CCL21 protein, human; D054421:Chemokine CCL21; D016207:Cytokines; D051020:bcl-X Protein; D013792:Thalidomide; D000077269:Lenalidomide