Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse

TY - JOUR

T1 - Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse

AU - Carlin, L M

AU - Yanagi, K

AU - Verhoef, A

AU - Hoen, E N M N

AU - Yates, J

AU - Gardner, L

AU - Lamb, J

AU - Lombardi, G

AU - Dallman, M J

AU - Davis, D M

PY - 2005/12/1

Y1 - 2005/12/1

N2 - We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3 epsilon and CD3 zeta initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact. In contrast, at synapses formed by anergized T cells, CD3 epsilon and CD3 zeta remained organized within an arc or ring and failed to redistribute centrally. However, intercellular communication between anergic human T cells and agonist peptide-loaded APCs was not a null event, since it triggered secretion of T-cell interferon gamma (IFN-gamma) but not, for example, inter-leukin 2 (IL-2). Thus, distinct organizations of CD3 at the T-cell IS correlate with different cytokine profiles; the mature IS formed by resting T cells correlates with their production of both IFN-gamma and IL-2, whereas the immature IS formed by anergic T cells seems able to facilitate IFN-gamma but not IL-2 production

AB - We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3 epsilon and CD3 zeta initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact. In contrast, at synapses formed by anergized T cells, CD3 epsilon and CD3 zeta remained organized within an arc or ring and failed to redistribute centrally. However, intercellular communication between anergic human T cells and agonist peptide-loaded APCs was not a null event, since it triggered secretion of T-cell interferon gamma (IFN-gamma) but not, for example, inter-leukin 2 (IL-2). Thus, distinct organizations of CD3 at the T-cell IS correlate with different cytokine profiles; the mature IS formed by resting T cells correlates with their production of both IFN-gamma and IL-2, whereas the immature IS formed by anergic T cells seems able to facilitate IFN-gamma but not IL-2 production

U2 - 10.1182/blood-2005-03-0996

DO - 10.1182/blood-2005-03-0996

M3 - Article

SN - 1528-0020

VL - 106

SP - 3874

EP - 3879

JO - Blood

JF - Blood

IS - 12

ER -