Deficient cytokine response of human allergen-specific T lymphocytes from humanized SCID mice and reconstitution by professional antigen-presenting cells.
BACKGROUND
Hu-PBL-SCID mice generated by the transfer of PBMCs from atopic individuals may provide a physiologic in vivo model for investigating human responses to allergens and potential approaches toward immunotherapy.


OBJECTIVE
This study was undertaken to investigate the functional activity and cytokine profile of human allergen-reactive T lymphocytes isolated from hu-PBL-SCID mice.


METHODS
PBMCs from allergic individuals were coinjected with allergen into SCID mice. Human lymphocyte migration and phenotype were established by reverse transcription-PCR and immunohistochemistry, IgE levels in sera were determined, and the frequency of allergen-reactive cytokine-producing T lymphocytes was established.


RESULTS
After immunization with allergen, specific IgE levels in hu-PBL-SCID sera were comparable with levels in donor sera. Although the majority of lymphocytes remained in the peritoneum, significant numbers of T lymphocytes were located in the spleen, where human IL-4, IL-5, and IFN-gamma messenger RNA expression was detected after stimulation with PHA and phorbol myristate acetate. Failure to induce cytokine production by human T lymphocytes isolated from the peritoneum and spleen of hu-PBL-SCID mice by allergen was reversed by stimulating with allergen in the presence of exogenously added IL-2 and antigen-presenting cells (APC), particularly CD14(+) monocytes. Under these conditions, allergen-reactive T cells expressed a T(H)2-like phenotype.


CONCLUSIONS
These data suggest that, after initial activation and induction of antibody production, human T lymphocytes enter a state of unresponsiveness, arising from a loss of human professional APC, in hu-PBL-SCID mice. The use of hu-PBL-SCID mouse models in studies on therapeutic approaches for allergy may benefit from the additional transfer of human professional APC.
Jarman
E R
ER
Clinical Research Unit, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Perschke
K
K
Montermann
E
E
Herz
U
U
Renz
H
H
Knop
J
J
Reske-Kunz
A B
AB
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D016513:Mice, SCID / Q000097:blood*; D010537:Peritoneum / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology
D000485:Allergens; D016207:Cytokines; D000939:Epitopes; D012333:RNA, Messenger; D007073:Immunoglobulin E