CORRESPONDENCE

What is trogocytosis and what is its purpose?

To the editor: lymphocytes, may directly or indirectly pathogens. Because of their mobility, Several reports have documented that influence the phenotype and function of lymphocytes could contribute to the spread lymphocytes can extract surface molecules the lymphocytes. From an evolutionary of pathogens within the host either through through the ‘immunological synapse’ from perspective, trogocytosis may have developed direct capture of the pathogen or its the antigen-presenting cells to which they are initially as a symbiotic arrangement: genome6 (for example, prions or human conjugated1. This phenomenon, which we leukocytes may be ‘feeding’ off other cell immunodeficiency virus) or of cell surface have called ‘trogocytosis’1 (from the ancient types in return for undertaking the defense viral receptors from other cells7. Greek trogo, meaning ‘gnaw’), involves the of the organism against pathogens. Because We believe trogocytosis may have first transfer of plasma membrane fragments lipids are the most energetically demanding appeared in very primitive organisms as from the presenting cell to the lymphocyte. components to generate, fragments of a way for specialized cell types to feed off

http://www.nature.com/natureimmunology Trogocytosis has been documented in T, B plasma membrane acquired by lymphocytes other cells. Subsequently, direct transfer of and natural killer cells both in vitro and in could contribute substantially to their regulatory molecules may have contributed vivo. Thus, this process may be important in metabolic balance, thereby increasing their to the establishment of intercellular the induction and regulation of immune capacity to proliferate. communications. Of course, lymphocyte responses, and possibly in the control of Trogocytosis could be a vector for activation through trogocytosis would have other cellular systems1. intercellular communication. Molecules appeared much later in evolution. The Trogocytosis corresponds to an active acquired during trogocytosis that might alter efficient use of available resources through transfer phenomenon that is triggered the lymphocytes’ activity include regulatory trogocytosis, as proposed here, indicates that specifically by antigen receptor signaling. molecules on either side of the plasma evolution may favor this process. Thus, its It occurs within minutes of conjugate membrane, such as extracellular (hormone relative physiological relevance, which is still formation between two live cells and receptors and costimulatory molecules) or unclear, is worth investigating. therefore cannot be the result of phagocytosis intracellular (signal transduction components of apoptotic bodies2–4. Trogocytosis by and transcription factors) components. The Etienne Joly & Denis Hudrisier cytotoxic T lymphocytes might contribute to acquired molecules (for example, ‘homing’ © Group 2003 Nature Publishing Institut Claude de Préval, U563 INSERM, CHU the selection of high-affinity T cells through receptors) could conceivably direct certain Purpan, Toulouse, France. the removal of antigenic complexes from lymphocyte functions, such as migration e-mail: [email protected] the presenting dendritic cells5 and to the to the appropriate injured tissues. elimination of cytotoxic T lymphocytes Lymphocyte activation may also be 1. Hudrisier, D. & Joly, E. Plasma membrane nibbling: all lymphocytes do it, but why? ELSO Gaz. 9, 1–5 (2002). through ‘fratricide’ after the acquisition of facilitated through trogocytosis by 2. Huang, J.F. et al. TCR-mediated internalization of major histocompatibility complex molecules prolongation of the engagement of antigen peptide-MHC complexes acquired by T cells. Science loaded with antigenic peptide recognized by receptors after separation of the antigen- 286, 952–954 (1999). 3. Stinchcombe, J.C., Bossi, G., Booth, S. & Griffiths, 2 their own T cell receptor . Such ‘fratricide’ presenting cell–lymphocyte conjugate. G.M. The immunological synapse of CTL contains a may not be physiological, however, as This process may occur either in endocytic secretory domain and membrane bridges. Immunity 15, 751–761 (2001). it only occurs when an extremely high vesicles or in folds of the plasma membrane 4. Hudrisier, D., Riond, J., Mazarguil, H., Gairin, J.E. & concentration of major histocompatibility if the formation of a membrane bridge Joly, E. Cutting edge: CTLs rapidly capture membrane complex class I–restricted antigenic peptide has occurred, as has been shown3. Such fragments from target cells in a TCR signaling-depen- 2 dent manner. J. Immunol. 166, 3645–3649 (2001). is added externally to the target cell . a phenomenon would also allow for the 5. Kedl, R.M., Schaefer, B.C., Kappler, J.W. & Marrack, We postulate that trogocytosis could integration and accrual of fractional P. T cells down-modulate peptide-MHC complexes on have a broader function in the biology stimulatory signals through successive APCs in vivo. Nat. Immunol. 3, 27–32 (2002). 6. Igakura, T. et al. Spread of HTLV-I between lympho- of lymphocytes. During trogocytosis, encounters with antigen-presenting cells. cytes by virus-induced polarization of the cytoskele- lymphocytes inherit many different Finally, trogocytosis may also have ton. Science 299, 1713–1716 (2003). 7. Tabiasco, J. et al. Acquisition of viral receptor by NK molecules from conjugating cells. Some of negative consequences. Active lymphocytes cells through immunological synapse. J. Immunol. these molecules, which are not transcribed by naturally spend time in close proximity to 170, 5993–5998 (2003).

NATURE IMMUNOLOGY VOLUME 4 NUMBER 9 SEPTEMBER 2003 815