Basic science for the clinician 56: inducible T-cell costimulator--the world of costimulation gets more complicated…and interesting.
They say that nothing is assured in this world but change. And this applies in a cynical way to immunology: nothing is assured--we can never rest with an assumption that we know it all because there are always more apparent complications when analyzing immune mechanisms (someday, perhaps we will arrive on a "grand scheme" that elegantly explains it all, just as our brethren in particle physics seek the Higgs boson and the completion of a better model--I am not holding my breath awaiting completion of our task!). In a recent article in this series, we explored CTLA4 as a counterregulator of the CD28-CD80/86 costimulatory pathway. However, treatment with CTLA4 does not entirely shutdown the immune system; engineering animals so that the CD28-CD80/86 pathway no longer functions does not prevent functional protective immune responses. Thus, there must be yet another pathway. And there is--an "inducible T-cell costimulator" (ICOS) is found on T cells (activated, not naive), which has a single ligand on antigen-presenting cells (ICOS ligand, B7-RP-1). The rapid induction of ICOS speaks to its importance in T-cell function; however, ICOS is more relevant to the stimulation of effector and memory T cells than is CD28 signaling. There are similarities and differences, interactions, and overlaps between the 2 pathways, some of which are very useful in understanding the immunopathogenesis of immune diseases.
Division of Rheumatology and Connective Tissue Research, Departments of Medicine, Pediatrics, and Molecular Genetics & Microbiology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. lensigal@gmail.com
Leonard H
LH
Sigal
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060889:Inducible T-Cell Co-Stimulator Protein