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Recall Helper T Cell Response

T Helper 1 Cell–resistant Allergic Susceptibility without Biasing Uncommitted CD4 T Cells

Department of Microbiology and Immunology; Allergy, Pulmonary and Critical Care Medicine and Rheumatology Divisions, Department of Medicine; Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee; Department of Immunology; and Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, Ohio

Correspondence and requests for reprints should be addressed to Mark Boothby, M.D., Ph.D., Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232–2363. E-mail: mark.boothby{at}mcmail.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. Furthermore, nothing is known about the kinetics of memory responses after inhalation of antigen or interplay between an allergen-specific memory helper T (Th) cell Th2 population and uncommitted or competing Th1 cells. To study these processes, T cell receptor–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: mucosal antigen • helper T cell 1/ helper T cell 2 • immunoregulation • allergic lung disease

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