A novel approach to detect donor/recipent immune responses between HLA-identical pairs.
Renal transplant rejection and graft versus host reactions between HLA genetically-identical sibling (HLAgi) donor/recipient (D/R) pairs are thought to result from minor histocompatibility antigen (mHAg) disparities. We have compared two methods of measuring HLAgi D/R T lymphocyte responses to "matured" dendritic cells: 1.) a modified Cylex assay of CD4(+) ATP levels (MLDC-ATP) versus 2.) (3)H-thymidine uptake (MLDC-(3)H). The MLDC-ATP kinetics peaked at 48 hours versus the MLDC-(3)H at 7 days, and appeared more sensitive. We tested HLAgi (normal) volunteer siblings (NLs), and D/R sibling pairs before and after renal transplantation (pre-Tx and post-Tx). The overall frequencies of positive responses in the MLDC-ATP for HLAgi NLs, pre-Tx, and post-Tx D/R pairs were 63%, 50%, and 42%, respectively. The percentage with reciprocal responses was 37.5%, 20%, and 22.22%, respectively. In one set of three HLAgi (NLs) siblings (two males and one female), there was a nongender-associated differential response. There was no MLDC correlation with class I MHC-associated mHAg (SSP) incompatibility, nor could some MLDC positive reactive pairs theoretically process the necessary HLA-class I restriction molecules for presentation of known (nanomeric) mHAg peptides. Speculatively, the MLDC reflects class II MHC-restricted mHAg reactions (not yet definable), with possible effects of other polymorphic (nonhistocompatibility) immune response genes, and thereby may be a useful measurement of CD4(+) T-cell HLAgi transplantation immunity.
Jin
Yide
Y
Lillian Jean Kaplan Renal Transplant Center of the Division of Transplantation of the Department of Surgery, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida 33101, USA. YJin@med.miami.edu
Hernandez
Ana
A
Fuller
Laphalle
L
Rosen
Anne
A
Cirocco
Robert
R
Esquenazi
Violet
V
Ciancio
Gaetano
G
Burke
George W
GW
Miller
Joshua
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D012737:Sex Factors; D035781:Siblings; D013936:Thymidine / Q000378:metabolism; D014181:Transplantation Immunology
D001324:Autoantigens; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D015778:Minor Histocompatibility Antigens; D000255:Adenosine Triphosphate; D013936:Thymidine