CD4

Synonyms: Cluster of differentiation CD4

by Assia Bassarova

Background

CD4+ T helper (Th) cells play a central role in the immune system and carry out multiple functions including activation, coordination, modulation, and regulation of innate and adaptive immune responses. These various functions of Th cells are necessary to attain effective immune responses against a variety of different pathogens, while maintaining self-tolerance and avoiding undesired attacks against self-tissues. The CD4 molecule is a 55-59 kDa glycoprotein, member of immunoglobulin superfamily that is associated with HLA class II antigen recognition. The epitope defines the helper-inducer subtype of T-cells. CD4 positive T cells are mainly cytokine secreting cells. The CD4 antigen is absent from immature thymocytes and is expressed during T-cell development. T-cells in thymus can be double CD4 and CD8 positive. CD4 is also expressed on monocytes and monocyte-derived cells such as histiocytes and Langerhans cells. About 45% of peripheral blood lymphocytes are CD4-positive. In lymphatic tissue, the CD4+ T-cells are seen in large numbers in the parafollicular zones, while scattered cells are found in the germinal centers and mantle zones (T follicular helper cells). CD4 is also demonstrated in splenic littoral cells and hepatic sinusoidal cells.
CD4 serves as receptor for human immunodeficiency virus (HIV).

Staining in normal cells/tissues

Thymocytes, helper / inducer T-lymphocytes, monocytes / macrophages, granulocytes and Langerhans cells. Normally, CD4 and CD8 are mutually exclusive.

Staining in tumors

  • CD4 is variably expressed in precursor T-lymphoblastic leukemia/lymphoma
  • Most mature T-cell lymphomas are CD4 positive with the exception of aggressive NK-cell leukaemia and extranodal NK/T-cell lymphomas: subcutaneous panniculitis-like T-cell lymphoma (which is usually CD8 positive), enteropathy-type T-cell lymphoma and hepatosplenic T-cell lymphoma
  • CD4 expression is observed in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
  • CD4 is also expressed in histiocytic sarcomas and Langerhans cell histiocytosis as well as in splenic littoral cell haemangioma

Staining pattern

Distinct membranous staining.

Control tissue

Appendix – compared to normal helper/inducer T-cells the macrophages generally express a weak CD4 staining. The capability to detect these cells verifies the sensitivity of the used protocol.

Application

  • Classification of lymphocytes, especially in inflammatory lesions and autoimmune processes
  • Classification of malignant lymphomas

Selected references

  1. Pepper M, Jenkins MK. Origins of CD4(+) effector and central memory T cells. Nat Immunol. 2011 Jun;12(6):467-71. doi: 10.1038/ni.2038. PMID: 21739668; PMCID: PMC4212218.
  2. Raphael I, Joern RR, Forsthuber TG. Memory CD4+T Cells in Immunity and Autoimmune Diseases. Cells. 2020;9(3):531. Published 2020 Feb 25. doi:10.3390/cells9030531
  3. von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000 Oct 5;343(14):1020-34. doi: 10.1056/NEJM200010053431407. PMID: 11018170.