Re: CD4/CD8 coexpression in pb

From: jose.diaz_romero@pharma.Novartis.com
Date: Thu Apr 13 2000 - 03:31:51 EST


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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