The development of primed/memory CD8+ lymphocytes in vitro and in rejecting kidneys after transplantation.
In normal individuals, 80 +/- 5% of circulating CD8+ T cells express CD45RA, and 20 +/- 7% of these cells express CD45R0 antigens. After activation, CD8+ cells expressing CD45RA decrease to 56-67% while those expressing CD45R0 increase to 38-67%. Although precursors of alloantigen-specific cytotoxic T cells were found in both CD8+, CD45RA+ and CD8+, CD45R0+ subsets, the specific effector cells were exclusively CD8+, CD45R0. Allospecific cytotoxic CD8+ clones were also entirely CD45R0+. A lectin-dependent cytotoxic (LDC) assay unmasked a hierarchy of killing after alloactivation which was CD8+, CD45R0+ greater than CD8+, CD45RA+ greater than CD4+, CD45R0+ greater than CD4+, CD45RA+. The phenotype of CD8+ T cells in rejecting kidneys was similar to in vitro alloantigen-activated CD8+, CD45R0+ cells and cytotoxic CD8+ clones. Firstly there was an increase in the relative proportions of CD45R0+ (60 +/- 8%) and a decrease in CD45RA+ (35 +/- 10%) CD8+ cells relative to circulating CD8+ subsets. In the rejecting grafts, 34 +/- 9% of the CD8+ cells were also DR+ indicative of recent activation. Furthermore, 16% (range 4-35%) of rejecting CD8+ cells were Ki67+ suggesting that these cells were proliferating. Finally, 17% (range 4-53%) of T cells in rejecting kidneys simultaneously expressed both CD45RA and CD45R0 markers. These results show that in vitro alloantigen-activated CD8+, CD45R0+ cells represent a primed/memory cytotoxic population. In addition, they provide indirect evidence that a proportion of CD8+ cells in rejecting kidneys were actively switching from a naive to a memory phenotype in vivo in a manner analogous to that in vitro.
Akbar
A N
AN
Department of Immunology, Royal Free Hospital School of Medicine, London, England.
Amlot
P L
PL
Timms
A
A
Lombardi
G
G
Lechler
R
R
Janossy
G
G
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D003601:Cytotoxicity Tests, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D066298:In Vitro Techniques; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D007519:Isoantigens; D017493:Leukocyte Common Antigens