Anti-CD3-induced anergy in cloned human Th0, Th1, and Th2 cells.

Abstract:

:In the mouse, activation of T cells by T cell receptor (TCR) crosslinking with anti-CD3 antibodies in the absence of a costimulatory signal induces Th1 but not Th2 cell anergy. Furthermore, anti-CD3 induces anergy of Th1- but not Th2-type lymphokine secretion in Th0 cells. This study was designed to determine whether this is also the case in man. Human rye grass allergen Lol p I-specific cloned CD4+ T helper cells of subtypes Th0, Th1, and Th2 were treated with immobilized anti-CD3. The cells were rested for 4 days and then activated under optimal conditions with antigen and antigen-presenting cells (APCs). Cell proliferation and IL-2, IFN-gamma, and IL-4 secretion was determined to test for the anergic state. The initial anti-CD3 treatment induced cell proliferation, IL-2, IFN-gamma, and/or IL-4 secretion by T cells of all three subsets which was followed by an anergic state in Th0, Th1, and Th2 cells as shown by a 51 to > 94% decrease in cell proliferation and IFN-gamma and/or IL-4 secretion after subsequent APC and Lol p I activation. Addition of IL-2 or IL-4 during anti-CD3 treatment of the cells did not prevent unresponsiveness. However, the addition of IL-2 but not IL-4 during APC and Lol p I stimulation partially reversed the anergic state. These data demonstrate that, contrary to the mouse, cloned T cells of all three human T helper cell subtypes are anergized by anti-CD3 TCR activation in the absence of costimulatory signals. The fact that human Th2 cells can be anergized may be important for the development of new treatments in Th2-mediated allergic disorders.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Nguyen DD,Beck L,Spiegelberg HL

doi

10.1006/cimm.1995.1199

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

153-7

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(85)71199-9

journal_volume

165

pub_type

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