Published ahead of print on November 14, 2003, doi:10.1164/rccm.200301-100OC Am. J. Respir. Crit. Care Med., Volume 169, Number 5, March 2004, 587-595 A more recent version of this article appeared on March 1, 2004
Submitted on February 6, 2003 Recall Th2 response: Th1-resistant allergic susceptibility without biasing uncommitted CD4 T cellsMark A Aronica1,1 Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical School, Nashville, TN, USA; Immunology, Cleveland Clinic Foundation, Cleveland, OH, USA, 2 Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN, USA, 3 Immunology, Cleveland Clinic Foundation, Cleveland, OH, USA, 4 Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical School, Nashville, TN, USA, 5 Pathology, Vanderbilt University School of Medicine, Nashville, TN, USA, 6 Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical School, Nashville, TN, USA; Rheumatology Divisions, Vanderbilt University Medical School, Nashville, TN, USA * To whom correspondence should be addressed. E-mail: mark.boothby{at}vanderbilt.edu.
Effector and memory T lymphocytes differ significantly, and there is no experimental evidence that memory cells are sufficient to render an otherwise normal individual susceptible to localized allergic inflammation. Further, nothing is known about the kinetics of memory responses after inhalation of antigen or interplay between an allergen-specific memory Th2 population and uncommitted or competing Th1 cells. To study these processes, TCR-transgenic CD4+ effector cells were generated in vitro, transferred into naive recipients, and allowed to resume a quiescent state. Inhalation of protein antigen reactivated these Ag-specific Th2 donor cells, leading to allergic pulmonary inflammation and airway hyperreactivity. Susceptibility was correlated with the size of the input Th2 population but Th1 cells neither enhanced nor reduced inflammation in this model. Importantly, the reactivation of these antigen-experienced cells by inhaled antigen did not skew the cytokine balance of recipient-derived T cells recruited to the lung, nor did it inhibit the development of donor-derived Th1 cells from uncommitted antigen-experienced cells that form a normal part of immune responses. These data indicate that a quiescent memory Th2 cell population can create susceptibility to allergic pulmonary inflammation in a manner refractory to inhibition by Th1 cells or endogenous inhibitory mechanisms. Key words: Airway hyperreactivity Memory T cells Immunoregulation Mucosal protein antigen
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