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Gene Review

CD8A  -  CD8a molecule

Homo sapiens

Synonyms: CD8, Leu2, MAL, T-cell surface glycoprotein CD8 alpha chain, T-lymphocyte differentiation antigen T8/Leu-2, ...
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Disease relevance of CD8A

  • A 25-year-old man, from a consanguineous family, with recurrent bacterial infections and total absence of CD8(+) cells, was studied [1].
  • Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS [2].
  • Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina [3].
  • T cell lines with a novel phenotype (CD3+ TCR-alpha/beta+ CD4- CD8-) were developed from the peripheral blood of a patient with a combined immunodeficiency and tissue injury resembling graft-vs-host disease [4].
  • The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice [5].

Psychiatry related information on CD8A

  • OBJECTIVE: To examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children [6].
  • Alcohol drinking, elevated CD8 lymphocyte counts and fluconazole therapy were associated with a decreased risk, and cigarette smoking with increased risk [7].
  • The psychological stress did lead to increases in the numbers of circulating CD8 suppressor/cytotoxic T cells and NK lymphocytes in old subjects to a similar degree as that seen in the young group [8].
  • Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months [9].
  • The CD4/CD8 ratio was low in all patients, but more so for BN patients, although cell-mediated immune function was impaired to the same extent for both eating disorders [10].

High impact information on CD8A

  • In a number of allogeneic transplant models (heart, skin, bone marrow) anti-CD4 (+/- CD8) antibodies can be shown to block the rejection process while selectively promoting the development of CD4+ regulatory T cells responsible for a dominant tolerance that is reflected in findings of linked suppression and infectious tolerance [11].
  • If allogeneic marrow is given at high cell doses under the umbrella of CD4 and CD8 antibodies, then tolerance can be achieved through clonal deletion [11].
  • Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor [12].
  • MAL N-terminal sequences, including two RPEL motifs, are required for the response to signaling, while other regions mediate its nuclear export (or cytoplasmic retention) and nuclear import [13].
  • Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution [14].

Chemical compound and disease context of CD8A


Biological context of CD8A


Anatomical context of CD8A


Associations of CD8A with chemical compounds

  • Leu-2/T8 is a cell surface glycoprotein expressed by most cytotoxic and suppressor T lymphocytes [22].
  • Thus, it appears that CD8 alpha may depend more on a protein kinase C-mediated signaling pathway, whereas CD4 may rely on greater tyrosine kinase activation [27].
  • Mutation of B- and F-strand cysteine residues in CD8 alpha reduced the ability of the protein to fold properly and, therefore, to be expressed [28].
  • Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes [29].
  • Flow cytometric analysis by using Indo-1 showed that coaggregation of CD4, CD8, and CD2 with CD3/TCR clearly enhances a minimal signal delivered via CD3/TCR on immature thymocytes [30].

Physical interactions of CD8A


Regulatory relationships of CD8A

  • There is convincing evidence that soluble HLA-A,-B,-C (sHLA-A,-B,-C) and soluble HLA-G (sHLA-G) antigens can induce apoptosis in CD8(+) activated T cells although there is scanty and conflicting information about the mechanism(s) by which sHLA-A,-B,-C antigens and sHLA-G antigens induce apoptosis [34].
  • RESULTS: We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks [35].
  • Interleukin-4 promotes human CD8 T cell expression of CCR7 [36].
  • Outgrowing lymphocytes were cloned, expanded in vitro, and 11 clones were subjected to phenotypic analysis: ten clones showed a predominantly CD4-positive T "helper/inducer" phenotype whereas one clone expressed CD8 T "cytotoxic/suppressor" antigens [37].
  • The human CD8 glycoprotein is expressed either as an alpha beta heterodimer or as an alpha alpha homodimer on thymocytes, mature T cells, and subpopulations of intestinal intraepithelial lymphocytes (IELs) [38].

Other interactions of CD8A


Analytical, diagnostic and therapeutic context of CD8A

  • Consistent with this data, antiphosphotyrosine immunoblotting revealed greater tyrosine phosphorylation of intracellular substrates after TCR/CD4 cross-linking compared with TCR/CD8 cross-linking [27].
  • We report the isolation of genomic and cDNA clones encoding the human T-lymphocyte cell-surface differentiation antigen, Leu-2 (T8), by use of a combination of transfection, fluorescence-activated cell-sorting, and subtractive cDNA hybridization [44].
  • In situ hybridization experiments revealed that CD8 and gamma/delta-TCR were not expressed by CD enterocytes [45].
  • The work reported here demonstrates that human multinegative (MN) thymocytes, depleted of cells bearing CD3, CD4, CD8, and CD19, express predominantly the high molecular mass CD45RA isoform, and lack low molecular mass CD45RB isoforms and CD45R0 as detected by immunofluorescence [46].
  • The data suggest that the tyrosine kinase p56lck (lck) plays a crucial role in determining lineage choice, in that maturation of thymocytes into the CD4 lineage occurs upon recruitment of active lck to the T-cell receptor (TCR)/CD3 complex, whereas CD8 maturation can be induced by CD3 ligation in the absence of co-receptor-mediated lck recruitment [47].


  1. Familial CD8 deficiency due to a mutation in the CD8 alpha gene. de la Calle-Martin, O., Hernandez, M., Ordi, J., Casamitjana, N., Arostegui, J.I., Caragol, I., Ferrando, M., Labrador, M., Rodriguez-Sanchez, J.L., Espanol, T. J. Clin. Invest. (2001) [Pubmed]
  2. Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Shuster, J.J., Falletta, J.M., Pullen, D.J., Crist, W.M., Humphrey, G.B., Dowell, B.L., Wharam, M.D., Borowitz, M. Blood (1990) [Pubmed]
  3. Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. Marschall, M., Marzi, A., aus dem Siepen, P., Jochmann, R., Kalmer, M., Auerochs, S., Lischka, P., Leis, M., Stamminger, T. J. Biol. Chem. (2005) [Pubmed]
  4. Double-negative (CD4- CD8-) T cells with an alpha/beta T cell receptor. Non-MHC-restricted cytolytic activity and lymphokine production. Brooks, E.G., Wirt, D.P., Goldblum, R.M., Vaidya, S., Asuncion, M.T., Patterson, J.C., Ware, C.F., Klimpel, G.R. J. Immunol. (1990) [Pubmed]
  5. T cells of atopic asthmatics preferentially infiltrate into human bronchial xenografts in SCID mice. Tsumori, K., Kohrogi, H., Goto, E., Hirata, N., Hirosako, S., Fujii, K., Ando, M., Kawano, O., Mizuta, H. J. Immunol. (2003) [Pubmed]
  6. Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children. Kharbanda, M., Than, S., Chitnis, V., Sun, M., Chavan, S., Bakshi, S., Pahwa, S. AIDS (2000) [Pubmed]
  7. Risk factors associated with Epstein-Barr virus replication in oral epithelial cells of HIV-infected individuals. Boulter, A.W., Soltanpoor, N., Swan, A.V., Birnbaum, W., Johnson, N.W., Teo, C.G. AIDS (1996) [Pubmed]
  8. Immunological changes in young and old adults during brief laboratory stress. Naliboff, B.D., Benton, D., Solomon, G.F., Morley, J.E., Fahey, J.L., Bloom, E.T., Makinodan, T., Gilmore, S.L. Psychosomatic medicine. (1991) [Pubmed]
  9. Prospective associations between lateralised brain function and immune status in HIV infection: analysis of EEG, cognition and mood over 30 months. Gruzelier, J., Burgess, A., Baldeweg, T., Riccio, M., Hawkins, D., Stygall, J., Catt, S., Irving, G., Catalan, J. International journal of psychophysiology : official journal of the International Organization of Psychophysiology. (1996) [Pubmed]
  10. Nutritional status and immunocompetence in eating disorders. A comparative study. Marcos, A., Varela, P., Santacruz, I., Muñoz-Vélez, A., Morandé, G. European journal of clinical nutrition. (1993) [Pubmed]
  11. How do monoclonal antibodies induce tolerance? A role for infectious tolerance? Waldmann, H., Cobbold, S. Annu. Rev. Immunol. (1998) [Pubmed]
  12. Regulation of lymphocyte function by protein phosphorylation. Perlmutter, R.M., Levin, S.D., Appleby, M.W., Anderson, S.J., Alberola-Ila, J. Annu. Rev. Immunol. (1993) [Pubmed]
  13. Actin dynamics control SRF activity by regulation of its coactivator MAL. Miralles, F., Posern, G., Zaromytidou, A.I., Treisman, R. Cell (2003) [Pubmed]
  14. Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution. Leahy, D.J., Axel, R., Hendrickson, W.A. Cell (1992) [Pubmed]
  15. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. Kovacs, J.A., Lempicki, R.A., Sidorov, I.A., Adelsberger, J.W., Herpin, B., Metcalf, J.A., Sereti, I., Polis, M.A., Davey, R.T., Tavel, J., Falloon, J., Stevens, R., Lambert, L., Dewar, R., Schwartzentruber, D.J., Anver, M.R., Baseler, M.W., Masur, H., Dimitrov, D.S., Lane, H.C. J. Exp. Med. (2001) [Pubmed]
  16. Cytotoxicity of sulfonamide reactive metabolites: apoptosis and selective toxicity of CD8(+) cells by the hydroxylamine of sulfamethoxazole. Hess, D.A., Sisson, M.E., Suria, H., Wijsman, J., Puvanesasingham, R., Madrenas, J., Rieder, M.J. FASEB J. (1999) [Pubmed]
  17. Human immunodeficiency virus type 2 envelope glycoprotein binds to CD8 as well as to CD4 molecules on human T cells. Kaneko, H., Neoh, L.P., Takeda, N., Akimoto, H., Hishikawa, T., Hashimoto, H., Hirose, S., Karaki, S., Takiguchi, M., Nakauchi, H., Kaneko, Y., Yamamoto, N., Sekigawa, I. J. Virol. (1997) [Pubmed]
  18. Spectrum of CD4 to CD8 T-cell ratios in lymphocytic alveolitis associated with methotrexate-induced pneumonitis. Fuhrman, C., Parrot, A., Wislez, M., Prigent, H., Boussaud, V., Bernaudin, J.F., Mayaud, C., Cadranel, J. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
  19. Chronic hypersensitivity pneumonitis in Japan: a nationwide epidemiologic survey. Yoshizawa, Y., Ohtani, Y., Hayakawa, H., Sato, A., Suga, M., Ando, M. J. Allergy Clin. Immunol. (1999) [Pubmed]
  20. Linkage of the murine transforming growth factor alpha gene with Igk, Ly-2, and Fabp1 on chromosome 6. Fowler, K.J., Mann, G.B., Dunn, A.R. Genomics (1993) [Pubmed]
  21. Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Kioussis, D., Ellmeier, W. Nat. Rev. Immunol. (2002) [Pubmed]
  22. The T cell differentiation antigen Leu-2/T8 is homologous to immunoglobulin and T cell receptor variable regions. Sukhatme, V.P., Sizer, K.C., Vollmer, A.C., Hunkapiller, T., Parnes, J.R. Cell (1985) [Pubmed]
  23. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Holoshitz, J., Koning, F., Coligan, J.E., De Bruyn, J., Strober, S. Nature (1989) [Pubmed]
  24. Variable-constant segment genotype of immunoglobulin kappa is associated with increased risk for rheumatoid arthritis. Moxley, G. Arthritis Rheum. (1992) [Pubmed]
  25. Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Gao, G.F., Tormo, J., Gerth, U.C., Wyer, J.R., McMichael, A.J., Stuart, D.I., Bell, J.I., Jones, E.Y., Jakobsen, B.K. Nature (1997) [Pubmed]
  26. Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. Sanders, S.K., Giblin, P.A., Kavathas, P. J. Exp. Med. (1991) [Pubmed]
  27. Evidence for differential intracellular signaling via CD4 and CD8 molecules. Ravichandran, K.S., Burakoff, S.J. J. Exp. Med. (1994) [Pubmed]
  28. Human CD8 beta, but not mouse CD8 beta, can be expressed in the absence of CD8 alpha as a beta beta homodimer. Devine, L., Kieffer, L.J., Aitken, V., Kavathas, P.B. J. Immunol. (2000) [Pubmed]
  29. Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes. Romero, P., Zippelius, A., Kurth, I., Pittet, M.J., Touvrey, C., Iancu, E.M., Corthesy, P., Devevre, E., Speiser, D.E., Rufer, N. J. Immunol. (2007) [Pubmed]
  30. Differential regulation of Ca2+ mobilization in human thymocytes by coaggregation of surface molecules. Deusch, K., Daley, J.F., Levine, H., Languet, A.J., Anderson, P., Schlossman, S.F., Blue, M.L. J. Immunol. (1990) [Pubmed]
  31. Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function. Yeung, R.S., Penninger, J.M., Kündig, T.M., Law, Y., Yamamoto, K., Kamikawaji, N., Burkly, L., Sasazuki, T., Flavell, R., Ohashi, P.S., Mak, T.W. J. Exp. Med. (1994) [Pubmed]
  32. Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3. Kieffer, L.J., Greally, J.M., Landres, I., Nag, S., Nakajima, Y., Kohwi-Shigematsu, T., Kavathas, P.B. J. Immunol. (2002) [Pubmed]
  33. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Salter, R.D., Norment, A.M., Chen, B.P., Clayberger, C., Krensky, A.M., Littman, D.R., Parham, P. Nature (1989) [Pubmed]
  34. Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Contini, P., Ghio, M., Poggi, A., Filaci, G., Indiveri, F., Ferrone, S., Puppo, F. Eur. J. Immunol. (2003) [Pubmed]
  35. Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-alpha inhibitors. Aeberli, D., Seitz, M., Jüni, P., Villiger, P.M. Rheumatology (Oxford, England) (2005) [Pubmed]
  36. Interleukin-4 promotes human CD8 T cell expression of CCR7. Seneviratne, S.L., Black, A.P., Jones, L., di Gleria, K., Bailey, A.S., Ogg, G.S. Immunology (2007) [Pubmed]
  37. Tumor-infiltrating lymphocytes isolated from a Ki-1-positive large cell lymphoma of the skin. Phenotypic characterization and analysis of cytokine secretion. Reinhold, U., Abken, H., Kukel, S., Goeden, B., Uerlich, M., Neumann, U., Kreysel, H.W. Cancer (1991) [Pubmed]
  38. Appropriate developmental expression of human CD8 beta in transgenic mice. Kieffer, L.J., Yan, L., Hanke, J.H., Kavathas, P.B. J. Immunol. (1997) [Pubmed]
  39. The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. Janeway, C.A. Annu. Rev. Immunol. (1992) [Pubmed]
  40. Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. Zemmour, J., Parham, P. J. Exp. Med. (1992) [Pubmed]
  41. A second subunit of CD8 is expressed in human T cells. Norment, A.M., Littman, D.R. EMBO J. (1988) [Pubmed]
  42. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Barber, E.K., Dasgupta, J.D., Schlossman, S.F., Trevillyan, J.M., Rudd, C.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  43. Extrathymic generation of tumor-specific T cells from genetically engineered human hematopoietic stem cells via Notch signaling. Zhao, Y., Parkhurst, M.R., Zheng, Z., Cohen, C.J., Riley, J.P., Gattinoni, L., Restifo, N.P., Rosenberg, S.A., Morgan, R.A. Cancer Res. (2007) [Pubmed]
  44. Isolation of the gene encoding the human T-lymphocyte differentiation antigen Leu-2 (T8) by gene transfer and cDNA subtraction. Kavathas, P., Sukhatme, V.P., Herzenberg, L.A., Parnes, J.R. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  45. Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes. Zimmer, K.P., Naim, H., Weber, P., Ellis, H.J., Ciclitira, P.J. FASEB J. (1998) [Pubmed]
  46. Prolonged expression of high molecular mass CD45RA isoform during the differentiation of human progenitor thymocytes to CD3+ cells in vitro. Deans, J.P., Wilkins, J.A., Caixia, S., Pruski, E., Pilarski, L.M. J. Immunol. (1991) [Pubmed]
  47. Molecular requirements for lineage commitment in the thymus--antibody-mediated receptor engagements reveal a central role for lck in lineage decisions. Basson, M.A., Bommhardt, U., Mee, P.J., Tybulewicz, V.L., Zamoyska, R. Immunol. Rev. (1998) [Pubmed]
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