OX40 (CD134) controls memory T helper 2 cells that drive lung inflammation.
Asthma is caused by memory Th2 cells that often arise early in life and persist after repeated encounters with allergen. Although much is known regarding how Th2 cells develop, there is little information about the molecules that regulate memory Th2 cells after they have formed. Here we show that the costimulatory molecule OX40 is expressed on memory CD4 cells. In already sensitized animals, blocking OX40-OX40L interactions at the time of inhalation of aerosolized antigen suppressed memory effector accumulation in lung draining lymph nodes and lung, and prevented eosinophilia, airway hyperreactivity, mucus secretion, and Th2 cyto-kine production. Demonstrating that OX40 signals directly regulate memory T cells, antigen-experienced OX40-deficient T cells were found to divide initially but could not survive and accumulate in large numbers after antigen rechallenge. Thus, OX40-OX40L interactions are pivotal to the efficiency of recall responses regulated by memory Th2 cells.
Salek-Ardakani
Shahram
S
La Jolla Institute for Allergy and Immunology, Division of Immunochemistry, 10355 Science Center Dr., San Diego, CA 92121, USA.
Song
Jianxun
J
Halteman
Beth S
BS
Jember
Amha Gebre-Hiwot
AG
Akiba
Hisaya
H
Yagita
Hideo
H
Croft
Michael
M
D000818:Animals; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018960:Hyaluronan Receptors / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018418:Th2 Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics* / Q000276:immunology*
D018960:Hyaluronan Receptors; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7