Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells

Bykovskaja, S.N.; Rytenko, A. N.; Rauschenbach, M.O.; Bykovsky, A.F.

doi:10.1016/0008-8749(78)90325-8

Cited by 51 publications

(9 citation statements)

References 19 publications

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“…We show that release occurs by exocytosis, whereby the granule membrane fuses with the CTL plasma membrane and dense cores and internal vesicles are externalized into the clefts. The presence of membraneous materials and dense material in clefts has been noticed before [20,53,551. In addition, we have observed that internal vesicles as well as dense cores can associate with the target cell membrane.…”

Section: Discussionmentioning

confidence: 93%

“…The cytolytic components which are contained within the core andor associated with the vesicles (manuscript in preparation) would be specifically delivered to the TC as result of binding of the vesicles and/or the core via TcR-MHC/ antigen interaction, followed by membrane fusion. Received March 20,1989; in revised form May 22, 1989. 5 References…”

Section: Discussionmentioning

confidence: 98%

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Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Peters¹,

Geuze²,

Donk³

et al. 1989

Eur J Immunol

232

146

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An ultrastructural analysis of human cytotoxic T lymphocyte-target cell (CTL-TC) interaction has been undertaken to enable a better understanding of the killing mechanism. Attention was focused on granules in the CTL, which are known to contain lethal compounds. Within the membrane-delimited cytotoxic granule an electron-dense core as well as numerous membrane vesicles were identified. In CTL-TC conjugates, specific membrane interactions take place, allowing the formation of intercellular clefts into which the granule cores and internal vesicles are released. T cell surface membrane molecules known to be involved in CTL-TC interaction (T cell receptor, CD3 and CD8) are present on the membranes of the granule cores and internal vesicles, facing outward. An explanation for this localization of the membrane may be found in the fact that the granule is connected with an endocytotic pathway. Moreover, the lumen of the granule is rich in the enzyme cathepsin D, which indicates an association with a lysosomal compartment. Exocytosed vesicles and cores are seen to adhere to the plasma membrane of the TC. Although the exact contents of the granule vesicles and core remain to be identified, we suggest that specific interaction of CTL membrane molecules on the cytolytic granule components with molecules on the plasma membrane of the TC may ensure the unidirectional delivery of the lethal hit.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Peters¹,

Geuze²,

Donk³

et al. 1989

Eur J Immunol

232

146

View full text Add to dashboard Cite

show abstract

“…Although it has been known for many years that extensive regions of interdigitations (Kalina and Berke, 1976; Sanderson and Glauert, 1977, 1979), flattened areas and secretory clefts (Bykovskaja et al, 1978; Carpen et al, 1982; Stinchcombe et al, 2001b) can form between killer cells and targets, the functional significance of these differences in membrane organisation has not been clear. Our studies reveal temporal and structural links between the accumulated actin and the extensive interdigitations between CTL and target.…”

Section: Discussionmentioning

confidence: 99%

Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL

Jenkins

Stinchcombe

Au-Yeung

et al. 2014

eLife

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T cell receptor (TCR) activation leads to a dramatic reorganisation of both membranes and receptors as the immunological synapse forms. Using a genetic model to rapidly inhibit Zap70 catalytic activity we examined synapse formation between cytotoxic T lymphocytes and their targets. In the absence of Zap70 catalytic activity Vav-1 activation occurs and synapse formation is arrested at a stage with actin and integrin rich interdigitations forming the interface between the two cells. The membranes at the synapse are unable to flatten to provide extended contact, and Lck does not cluster to form the central supramolecular activation cluster (cSMAC). Centrosome polarisation is initiated but aborts before reaching the synapse and the granules do not polarise. Our findings reveal distinct roles for Zap70 as a structural protein regulating integrin-mediated control of actin vs its catalytic activity that regulates TCR-mediated control of actin and membrane remodelling during formation of the immunological synapse.DOI: http://dx.doi.org/10.7554/eLife.01310.001

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“…Several authors have noted projections from the effector cells pushing into the target cell (Kalina & Hollander, 1975;Kalina & Berke, 1976, Ryser et al, 1977Searle & Flaks, 1976;Sanderson & Glauert, 1977;Bykovskaja et al, 1978). A study of material fixed at 37 O C within 10 min of contact, under conditions giving very high rates of killing, has permitted a detailed description of these projections (Sanderson & Glauert 1979).…”

Section: ( 6 ) Specialized Projections From T C Cellsmentioning

confidence: 99%

The Mechanism of Lymphocyte‐mediated Cytotoxicity

Sanderson

1981

Biological Reviews

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Summary 1. Three classes of cytotoxic lymphocyte are discussed: thymus‐derived T cells, antibody‐dependent K cells and NK (natural killer) cells. Each of these cytotoxic lymphocytes has receptors allowing the formation of adhesions (contact) with a target cell (the cell to be killed). The type of receptor and the corresponding ligand on the target cell is different in each class. Cytotoxic T cells (and probably NK cells) react with a target cell antigen, in a manner rather like antibody‐antigen reactions (although not involving classical serum antibody). K cells have a receptor for the Fc part of immunoglobulin (IgG) and hence can make contact with antibody‐coated target cells. 2. It seems likely that all three classes of cytotoxic lymphocyte have a similar basic mechanism of killing, which is different from the membrane leakage occurring in complement‐mediated lysis. Much more information is available on cytotoxic T cells than on the other types of cell. 3. Cytotoxic T cell killing can be divided into two phases. A reversible phase in which the T cell is in contact with the target cell, but causes no apparent damage. This phase can vary from a few minutes up to several hours, when a single T cell interacts with a single target cell. If the T cell detaches or is inactivated the target cell survives. The second phase is irreversible, once the lethal event has occurred, and the target cell will progress to eventual lysis in the absence of the Tc cells. 4. The lethal event initiates a period of zeiosis (membrane blebbing) in the target cell, which is accompanied by increased effiux of 86rubidium. Cell lysis occurs at a variable time after the initiation of zeiosis, when the soluble contents of the cytoplasm burst out of the target cell. The fact that both these phases are of variable length leads to the accumulation of cytoplasmic markers (such as 51chromium) in the medium in an approximately linear fashion. 5. The nature of the lethal event is unknown, but it is suggested that it involves changes inside the target cell rather than at the target cell membrane. Remarkable long projections from the T cell (and also seen from K cells and NK cells), apparently arising as a result of the receptor‐ligand interaction, may be involved in the delivery of the lethal event.

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Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells

Cited by 51 publications

References 19 publications

Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL

The Mechanism of Lymphocyte‐mediated Cytotoxicity

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