ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY (1999) 17:93-99
Frequencies of Cytotoxic T Lymphocyte
Precursor Estimate in Three Different
Khawaja Haque" Carol Truman" Ian Dittmer2,3, Patricia Denning-Kendall" Jill Hows1 and
Allogeneic graft rejection is
T cell dependent and thus T cells
playa central role in immunological
graft rejection. The reactivity of the
T cells is directed against major
histocompatibility complex (MHC)
and/or minor histocompati bility
complex (mHC). I Naive or memory
T cells are incapable of killing tar
get cells directly and are therefore
referred to as CTLp to denote their
inactive state. The naive T cells are
present at orders of magnitude
higher than other sUb-populations of
T cells. those directed to nominal
antigens directly recognize MHC
alloantigens and are responsible for
the extraordinary strength of
allograft responses. I,2 An alloreac
tive CTLp has the potential to dif
ferentiate into a clone of activated
CTL after engaging the specific
alloantigen recognized by its T cell
SUMMARY There is speculation that high cytotoxic T lymphocyte precur
sor frequencies (CTLpf) correlate with poor clinical outcome of bone
marrowlorgan transplantation. It is also believed that human umbilical
cord blood is immunologically naive, and, therefore cord blood T cells
may be less able to mediate graft versus host disease than marrow
derived T cells. CTLpf were determined in peripheral blood mononuclear
cells collected from healthy adults, human umbilical cord blood and renal
dialysis patients who were randomly selected and entered into this study.
A highly sensitive non-radioactive Europium release cytotoxicity assay
was optimized and modified to carry out the CTLpf estimation by using
the principle of limiting dilution analysis. The results of CTLpf in healthy
adults ranged from 1/694 to 1/66,666, median 1/7,339 (n=10); cord blood
ranged from 1/1,562 to 1/35,714, median 1/10,162 (n=6) and dialysis pa
tients ranged from 1/1,054 to 1/17,857 median 115,208 (n=9). The results
demonstrated that there is little difference of CTLpf median values
between the groups, but there is a wide variation of CTLpf between
individuals within a population. It suggests that this variation should be
taken into account when considering CTLpf assay as pre-transplantation
The existence of differences
in CTLpf against different HLA
class-I antigens has been demon
strated among unrelated healthy
individuals 4 In vitro CTLp res
ponses to mHC antigen have been
detected after in vivo sensitisation
by multiple blood transfusions in
patients with severe aplastic ane
mia. s Kaminski and co-workers also
showed a significant correlation bet
ween high CTLpf against the
recipient and the severity of acute
graft versus host disease (GVHO)
after 'matched' unrelated bone mar
row transplantation (BMT). Recent
reports supported the above findings
and showed that major variants
exist in alloreactive CTLpf against
HLA class I antigens in humans.
From the 'Division of Transplantation Sci·
ences, University of Bristol, 2Richard Bright
Renal Unit, Southmead Health Services, Bris
tol BS10 5NB, UK and 3Renal Unit, Auckland
Hospital, AUCkland, New Zealand.
Correspondence: Khawaja M.G. Haque
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