CD 27, CD28

CD27

Also called tumor necrosis factor receptor superfamily member 7

Binds to CD70

Marker of T cell activation; also regulates B cell activation and immunoglobulin synthesis

Uses: help differentiate memory-type CD8+ T cells (CD27+) from effector-type CD8+ T cells (important against pathogens, CD27-); memory B cells (CD27+) from naïve B cells (CD27-)

Positive staining (normal): T cells, memory B cells, NK cells, plasma cells, medullary thymocytes

Positive staining (disease): myelomas (64%, Br J Haematol 2006;132:168)

Negative staining: hairy cell leukemia (Haematologica 2005;90:266)

References: OMIM 186711




CD28

T cells require 2 signals for full activation - the first by binding of the antigen/MHC complex on antigen presenting cell to the T cell receptor; the second is delivered by the interaction of CD28 with its ligands CD80 (B7-1) or CD86 (B7-2), found on activated B cells, and is called a costimulation signal (diagram of 2 signals)

However, “superantagonistic” anti-CD28 antibodies, awaiting clinical trials for autoimmune diseases, activate mature T cells with only one signal (Ann Rheum Dis 2005;64 Suppl 4:iv91)

The costimulatory signal induces T cell activation and survival, interleukin-2 production, T-helper type 2 development and clonal expansion

CD28 is a constitutive, high abundance, low affinity receptor; its binding also increases expression of CTLA4 (CD152), a structurally related cell surface receptor on T cells which has the same ligands but opposite effects (J Clin Immunol 2002;22:1, Curr Pharm Des 2006;12:149); CTLA4 competes with CD28 for the same ligands (diagram)

Imbalance in CTLA-4/CD28 expression at the maternal-fetal interface may confer susceptibility to unexplained pregnancy loss (Int J Gynaecol Obstet 2006;93:123)

CD8+, CD28+ T cells: antigen specific cytotoxic T cells (class I restricted) (90% of CD8+ T cells)

CD8+, CD28- T cells: suppressor T cells; increased in various infectious diseases and autoimmune diseases and associated with aging Loss of T cell CD28 expression is associated with aging, and frequency of CD28(null) T cells predicts immune incompetence in elderly; these T cells are functionally active and long-lived, but have no/limited proliferative capacity (Immunol Rev 2005;205:158)

Uses: no significant clinical use by pathologists

Positive staining (normal): CD4+ T cells (95%), CD8+ T cells (50%); activated B cells, plasma cells (some)

Positive staining (disease): myeloma (95%)

References: OMIM 186760, Blood 2005;105:13