The development of primed/memory CD8+ lymphocytes in vitro and in rejecting kidneys after transplantation


Dr Arne Akbar. Department of Immunology. Royal Free Hospital School of Medicine. Pond Street. London NW3 2QG, UK.


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 CDS+, 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+ > CD8+, CD45RA+ > CD4+, CD45R0+ > CD4+, CD45RA+, The phenotype of CDS+ T cells in rejecting kidneys was similar to in vitro alloantigenactivated CDS+, 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.