OX40 (CD134) controls memory T helper 2 cells that drive lung inflammation

Shahram Salek-Ardakani, Jianxun Song, Beth S. Halteman, Amha Gebre-Hiwot Jember, Hisaya Akiba, Hideo Yagita, Michael Croft

Research output: Contribution to journalArticlepeer-review

213 Scopus citations


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 cytokine 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.

Original languageEnglish (US)
Pages (from-to)315-324
Number of pages10
JournalJournal of Experimental Medicine
Issue number2
StatePublished - Jul 21 2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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