Granule exocytosis by cytotoxic T lymphocytes generated in vivo

Munger, William E.; Berrebi, Gabriel; Henkart, Pierre A.

doi:10.1016/s0769-2625(87)80083-1

Cited by 11 publications

(3 citation statements)

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“…It was also found that the cell-associated TSP-1 is secreted into the extracellular space upon contact of virusspecific Ly-2' CTL with appropriate target cells (M. M. Simon et al, unpublished and [ll]). These data are in line with a recent study by Munger et al [45] on the expression and secretion of serine proteinase from in vivo primed alloreactive CTL derived from peritoneal exudates but oppose those from two other groups in which low or only marginal proteinase (esterase) activities were detected in similar sources of in vivo primed alloantigen specific CTL [46, 471. At present it is not possible to reconcile these contrasting results particularly since the latter groups have analyzed comparable T effector populations.…”

Section: Discussionsupporting

confidence: 91%

Induction of T cell serine proteinase 1 (TSP‐1)‐specific mRNA in mouse T lymphocytes

Simon¹,

Fruth²,

Eckerskorn

et al. 1988

Eur J Immunol

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An oligonucleotide probe corresponding to nucleotides of a cDNA encoding the T cell-associated proteinase 1 (TSP-1) was chosen to study the induction and expression of TSP-1-specific transcripts in mouse T lymphocytes and tissues. We demonstrate that TSP-1 mRNA is only expressed in activated T lymphocytes and is absent from all mouse tissues tested including those containing resting mature T lymphocytes. Expression of the TSP-1 gene was observed in T lymphocytes in vitro in response to either phorbolester (phorbol 12-myristate 13-acetate), Ca2+ ionophore (A23187), lectin or alloantigen. In general, TSP-1 mRNA appeared and peaked later compared to interleukin 2 transcripts. Furthermore, TSP-1 mRNA was inducible in vitro in both Ly-2+ and L3T4+ lymphocyte populations treated with alloantigen and/or lectin. The transcription of the TSP-1 gene was always accompanied by the expression of proteinase activity. High expression of TSP-1 transcripts was also observed in in vivo derived T effector cells specific for lymphocytic choriomeningitis virus. However, TSP-1 mRNA was predominantly associated with virus-specific Ly-2+ T cells and correlated with their proteinase and cytolytic activities. The data suggest that TSP-1 gene transcription is a useful marker to characterize T effector cells in vitro and in vivo.

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Section: Discussionsupporting

confidence: 91%

Induction of T cell serine proteinase 1 (TSP‐1)‐specific mRNA in mouse T lymphocytes

Simon¹,

Fruth²,

Eckerskorn

et al. 1988

Eur J Immunol

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“…Previous studies with human LGL (Zalman et al 1986a) and NK cells ) have also shown that these cells acquire PFP/C9-related protein only following in vitro stimulation with IL-2. On the other hand, it should be noted that Munger et al (1987) were able to detect both cytotoxicity and PFP/cytolysin in primary alloimmune PEL. These findings suggest that it is possible that perforin may only be expressed //; vivo under certain conditions of intense tissue stimulation and/or inflammation that would result in sustained high local IL-2 concentrations.…”

Section: Distribution Of Perforin In Various Tissues and Cell Types Amentioning

confidence: 89%

Perforin‐Dependent and ‐Independent Pathways of Cytotoxicity Mediated by Lymphocytes

Young

Liu

Persechini

et al. 1988

Immunological Reviews

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There is little doubt at the present time that both perforin-dependent and -independent pathways are important in mediating the cytotoxicity associated with lymphocytes. The cell distribution of perforin, initially thought to include both CTL and NK cells, now must be viewed with caution because all previous biochemical studies on CTL have been conducted with cell lines propagated in long-term cultures in the presence of T cell growth factors (IL-2 and perhaps some still undefined factors). Under these conditions, CTL are known to assume a broader, NK-like specificity in target cell killing and may thus differ significantly from primary CTL generated in the body. Accordingly, perforin does not seem to be present in primary CTL activated directly through mixed lymphocyte reactions. It remains to be shown how primary CTL lyse target cells in vivo. Initial studies conducted in several laboratories have already provided some clues. It now seems that even in cultured, perforin-containing CTL, the perforin pathway is not an obligatory mechanism required for target cell killing. Other pathways, possibly involving TNF/lymphotoxin-like molecules, may play a direct role in this type of cytotoxicity. Other still unidentified factors now also need to be sought, including membrane polypeptides that may develop cytotoxicity directly upon cell contact and binding. Although from the studies reviewed here it is clear now that perforin has a more limited role in cell killing than originally proposed, it is still intriguing that it should share structural and functional homologies with complement proteins, drawing paradoxical analogies between two systems (the cellular and the humoral immune systems) which have evolved to become specialized to carry out separate immunological tasks. The cloning of the genes for perforin and for all the C proteins that comprise the MAC should reveal important information on how these genes originated and then diverged during evolution. The cellular distribution of other granule products, such as serine esterases, also must be viewed with caution. A serine esterase activity was initially thought to be CTL-specific. This information stimulated an intensive research activity in many laboratories that resulted in both the purification of a serine esterase family and the cloning of several serine esterase transcripts. It is becoming clear from recent evidence that this group of enzymes is not truly CTL-specific and therefore would not be expected to develop any function rendered absolutely necessary for cytolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…He furthermore found that CTLs generated in primary MLC reactions had granules with serine esterase activity, but no hemolytic cytotoxin activity. Although Munger et al (1987) reported finding low levels of hemolytic activity in primary PELs. the possibility must be considered that this may have been due to contamination with a small number of granule-bearing cells.…”

Section: Introductionmentioning

confidence: 96%