Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.
Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.
Lord
G M
GM
Imperial College School of Medicine, Department of Immunology, The Hammersmith Hospital, London, UK.
Matarese
G
G
Howard
J K
JK
Baker
R J
RJ
Bloom
S R
SR
Lechler
R I
RI
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D020738:Leptin; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D011506:Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D013217:Starvation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D002352:Carrier Proteins; D007376:Interleukin-2; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D015847:Interleukin-4; D007371:Interferon-gamma