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
This archive was generated by hypermail 2b29 : Wed Apr 03 2002 - 11:55:43 EST