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Human Delayed-Type Hypersensitivity Reaction in a SCID Mouse Engrafted with Human T Cells and Autologous Skin

1996; Elsevier BV; Volume: 107; Issue: 4 Linguagem: Inglês

10.1111/1523-1747.ep12582823

1523-1747

Peter Petzelbauer, Marion Gröger, Rainer Kunstfeld, Elisabeth Petzelbauer, Klaus Wolff,

CAR-T cell therapy research

We have developed an animal model to study human delayed-type hypersensitivity reactions occurring in a human environment within a mouse host.Human skin was grafted onto the backs and autologous human immune cells were injected into the peritoneal cavity of mice with severe combined immunodeficiency.Seven and 14 d after grafting, 2-S0% of total white blood and spleen cells were of human origin.Mouse spleen-derived human T cells from tetanus toxoid-sensitized donors proliferated in response to tetanus toxoid as measured by [3H]thymidine uptake, and the strength of this proliferative response equaled that with pre-graft T cells &om the same donor.Proliferation was blocked with monoclonal antibodies t o h uman but not to mouse major histocompatibility complex antigens and with anti-human CD4 monoclonal antibodies.III lliuo vaccination of E x perime ntal procedures t o e lu c idate th e pathogen es is of infl amm a to ry r eacti o n s in h u mans ill II ivo are limi ted .b y techni cal , e thi c al , a nd h ea lth-re la te d con straints.Efforts h ave th e re for e b een m ad e to study th e hum a n immune sys te m unde r exp e rime nta l c onditions ill II jlro o r , alte m ative ly, to u se sm all animal m o d e ls ill IIjllo.A lth o u g h th e info rm atio n co n ce rnin g m o lecul es and cell s th at regul at e inflamm ato r y r e ac ti o n s ga in e d b y thi s appro ac h is co n sid e rabl e , it is b ased o n an alogies and is t h e refo re n e ith e r co mpre h e n sive n o r e ntire ly co rrect.Pro ble m s ari se mainl y £i'o m th e fac t th a t d evelo pme nta l difFe re n ces b e tw een hum an s and ro d e nts h a mpe r a di rec t co mpa riso n o f hum an and m o u se path o logy.C ertain surfa ce receptors fo und in hum an s arc n o t ex pressed in mi ce, and , m os t imp o rtantl y, cer ta in hum an di seases arc n ot fo und in ro d e nts.W e h ave th e refo re d eve lo p e d an a nim al m o d e l that o v e rco m es th e sp ecies barri e r b y u sin g hum an immune c e lls and au to logo u s human skin g rafte d o nto mi ce w ith seve re co mbin e d immun o d e fi c ie n cy (SCI D) to stud y human d e la ye d-typ e h yp e rse n siti v ity (DT I-I ) re actio n s occ urrin g in a hum an e n v iro nm ent w ithin a m o u se h ost.I-Ie re we sh ow tha t hum a n T cell s g ra fted into SCID mi ce b y Manu script rece ived