Mechanisms of deficient interferon-gamma production in atopic diseases.
BACKGROUND
The mechanisms responsible for an imbalanced cytokine response in atopic diseases are still not understood. While impaired interferon-gamma (IFN-gamma) production may be the result of a pathological T-cell/antigen-presenting cell (APC) interaction, evidence was provided that the T cell itself may have an intrinsic defect to produce IFN-gamma.


OBJECTIVE
To clarify whether impaired IFN-gamma production by T cells from patients with atopic dermatitis (AD) represents an intrinsic defect in producing IFN-gamma.


METHODS
Effector T cells were generated from CD4+ CD45RA+-naive precursors from patients with AD and healthy control individuals by activation with anti-CD3+ anti-CD28 MoAbs. Following restimulation, IFN-gamma production was measured by ELISA and flow cytometry.


RESULTS
IFN-gamma production by atopic T cells was decreased compared with healthy T cells. IL-12 present at priming or high doses of IL-2 during the culture period, even in the absence of IL-12, completely restored IFN-gamma production. Conversion of naive CD45RA+ to CD45R0+ effector cells did not differ between atopic and healthy donors' T cells.


CONCLUSIONS
Impaired IFN-gamma production by T cells from atopic individuals is not the result of an intrinsic, genetically fixed, defect to produce sufficient amounts of IFN-gamma. The data provides evidence that correction of an impaired TH1 response in AD may be successful at the precursor T cell level.
Jung
T
T
Department of Dermatology, Göttingen University, Göttingen, Germany.
Moessner
R
R
Dieckhoff
K
K
Heidrich
S
S
Neumann
C
C
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens