My two cents
We have found constant and significant numbers of CD4+/CD8+ cells in the pb
of normal individuals using the Lymphogram test (~1%, range 0.6 - 2.8%, n=
21). While it may be easier to explain these populations as background or
aggregates, I concure with Jose that this is a real population that can
fluxuate with various disorders.
see
Rapid and Simple Imunophenotypic characterization of Lymphocytes Using a New
Test. Bellido, M. et al. Haematologica 83: (8) pp 681-685. 1998.
Lymphogram has numberous advantages over conventional methods (for any one
interested see http://www.exalpha.com/lymphogram.htm for a complete
discription of the test and a comparison v. standard methods for CD4 and CD8
measurements).
Regards,
John Castracane
Exalpha Biologicals, Inc
In a message dated 4/13/00 3:19:41 PM, jose.diaz_romero@pharma.Novartis.com
writes:
<<
In peripheral blood, according to the classical scheme of
T-cell
differentiation, mature CD4+ and CD8+ T-cells are mutually exclusive
subsets.
However, mature T-cells with double-positive phenotype (CD4+/CD8+) can be
found
in very small numbers (1-3%) in human, and rat peripheral blood, and in a
higher
percentage, up to 15%, in rhesus monkeys (Macaca mulatta), cynomolgus
monkeys (
Macaca fascicularis) and African green monkeys (Cercophitecus aethiops).
In
normal adult pigs, a substantial proportion (10-60%) of peripheral
lymphocytes
can simultaneously express CD4 and CD8. Coexpression of CD4 and CD8 can
be
generated in peripheral blood T-cells by treatment with lectin which induces
CD8
a biosynthesis and cell surface expression. The CD4+/CD8+ population
derives
from CD4+/CD8- T-cells that become double positive upon activation.
Rabinowitz, R., R. Hadar, and M. Schlesinger. 1997. The appearance of
the
CD4+CD8+phenotype on activated T cells: possible role of antigen
transfer.
Hum.Immunol. 55:1.
Morris, D.L. and W.J. Komocsar. 1997. Immunophenotyping analysis
of
peripheral blood, splenic, and thymic lymphocytes in male and female
rats.
J.Pharmacol.Toxicol.Methods 37:37.
Zuckermann, F.A. and R.J. Husmann. 1996. Functional and phenotypic
analysis
of porcine peripheral blood CD4/CD8 double-positive T cells. Immunology
87:500.
Currier, J.R., Stevenson, K.S., Kehn, P.J., Zheng, K., Hirsch, V.M.
and
Robinson, M.A. (1999) Contributions of CD4+, CD8+, and CD4+CD8+ T cells
to
skewing within the peripheral T cell receptor beta chain repertoire of
healthy
macaques. Hum.Immunol. 60:209.
Ramirez, F., A.J. McKnight, A. Silva, and D. Mason. 1992.
Glucocorticoids
induce the expression of CD8 alpha chains on concanavalin A-activated rat
CD4+ T
cells: induction is inhibited by rat recombinant interleukin 4. J.Exp.Med.
176
:1551.
O'Donovan, M.R., S. Johns, and P. Wilcox. 1995. The effect of PHA
stimulation
on lymphocyte sub-populations in whole- blood cultures. Mutagenesis 10:371.
Paliard, X., R.W. Malefijt, J.E. de Vries, and H. Spits. 1988.
Interleukin-4
mediates CD8 induction on human CD4+ T-cell clones. Nature 335:642.
Elevated levels of peripheral double-positive cells have previously
been
reported in one apparently normal adult male, and this phenotype appear to
be
increased in a number of clinical conditions, including myasthenia
gravis,
multiple sclerosis, idiopathic thrombocytopenic purpura, Behcet?s
syndrome,
HIV-infection, inflammatory bowel disease, Kawaski disease, lepramatous
leprae,
and patients suffering some types of neoplasia.
Kay, N.E., N. Bone, M. Hupke, and A.P. Dalmasso. 1990. Expansion
of a
lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in
the
peripheral blood of a normal adult male. Blood 75:2024.
Hirao, J. and K. Sugita. 1998. Circulating CD4+CD8+ T lymphocytes
in
patients with Kawasaki disease. Clin.Exp.Immunol. 111:397.
Senju, M., K.C. Wu, Y.R. Mahida, and D.P. Jewell. 1991. Coexpression
of
CD4 and CD8 on peripheral blood T cells and lamina propria T cells
in
inflammatory bowel disease by two colour immunofluorescence and flow
cytometric
analysis. Gut 32:918.
Mizuki, M., S. Tagawa, T. Machii, M. Shibano, E. Tatsumi, K. Tsubaki,
H.
Tako, A. Yokohama, S. Satou, J. Nojima, T. Hirota, and T. Kitani.
1998.
Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T
lymphoid
leukemia. Leukemia 12:499.
Ottenhoff, T.H., D.G. Elferink, P.R. Klatser, and R.R. de Vries.
1986.
Cloned suppressor T cells from a lepromatous leprosy patient
suppress
Mycobacterium leprae reactive helper T cells. Nature 322:462.
Weiss, L., A. Roux, S. Garcia, C. Demouchy, N. Haeffner-Cavaillon,
M.D.
Kazatchkine, and M.L. Gougeon. 1998. Persistent expansion, in a
human
immunodeficiency virus-infected person, of V beta-restricted CD4+CD8+
T
lymphocytes that express cytotoxicity-associated molecules and are committed
to
produce interferon-gamma and tumor necrosis factor-alpha.
J.Infect.Dis.
178:1158.
Watanabe, N., S.C. De Rosa, A. Cmelak, R. Hoppe, L.A. Herzenberg, and
M.
Roederer. 1997. Long-term depletion of naive T cells in patients treated
for
Hodgkin's disease. Blood 90:3662.
Senju, M., K.C. Wu, Y.R. Mahida, and D.P. Jewell. 1991. Coexpression
of
CD4 and CD8 on peripheral blood T cells and lamina propria T cells
in
inflammatory bowel disease by two colour immunofluorescence and flow
cytometric
analysis. Gut 32:918.
Jose Diaz Romero
Transplantation Deparment
Novartis Pharma AG
Basel
Switzerland
>>
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