An analysis of the relationship between gamma delta T cell receptor V gene usage and non-major histocompatibility complex-restricted cytotoxicity

Our plain-English summary of An analysis of the relationship between gamma delta T cell receptor V gene usage and non-major histocompatibility complex-restricted cytotoxicity, by N. Mavaddat, B.W. Robinson, A.H. Rose, et al (Immunology and Cell Biology, 1993).

The study

• Authors: N. Mavaddat, B.W. Robinson, A.H. Rose, L.S. Manning, M.J. Garlepp
• Journal: Immunology and Cell Biology
• Published: 1993;71 ( Pt 1):27-37
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

gamma delta T cells are capable of mediating non-major histocompatibility complex (MHC) restricted lysis of a variety of tumour cell lines. The mechanism of this lysis and its significance in tumour immunity are not clear. We have used a panel of five malignant mesothelioma (MM) cell lines, as well as standard tumour targets K562 and Daudi, to investigate some of the factors which could be involved in non-MHC restricted cytotoxicity mediated by gamma delta T cells. Individual MM cell lines, representing a panel of lines derived from a single cell type, varied in their susceptibility to lysis by gamma delta T cell clones. Individual gamma delta T cell clones also showed unique cytotoxic profiles, and differed in their cytotoxic potential. T cell receptor (TCR) V gamma gene usage correlated with the ability of clones to lyse Daudi or K562; clones lysing Daudi expressing V gamma 9 and clones lysing K562 expressing V gamma I subgroup genes. No strict correlation between V gamma and V delta gene usage and MM reactivity was, however, demonstrable. There was also no correlation between gamma delta T cell lysis of MM cell lines and the capacity of gamma delta T cells to produce interferon-gamma, tumour necrosis factor-alpha, interleukin-2 or interleukin-4, nor with their expression of CD8.

In plain English

This was a laboratory study of immune cells called gamma delta T cells and their ability to kill tumour cells grown in the lab. The authors grew clones of these cells from the blood of three healthy adult donors, from lung lavage cells of one subject, and from lung tissue of three patients having lung surgery for cancer. They tested the clones against five malignant mesothelioma cell lines and two standard tumour lines, K562 and Daudi. The study did not examine asbestos exposure. Clones using a receptor gene segment called V gamma 9 killed Daudi but not K562. Clones that killed K562 generally used the V gamma I group. Killing of the mesothelioma lines was more complex. Every line except DeH(m) was highly susceptible to several clones, and NO36 was killed by 11 of the 12 clones tested. No strict link was found between killing of mesothelioma cells and receptor gene usage, cytokine production or CD8 expression. The authors concluded that killing is influenced by the properties of individual tumour lines, even within a single tissue type.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study of cloned human gamma delta T cells tested for killing of tumour cell lines
• Who was studied: Gamma delta T cell clones (15 listed in Table 1) derived from blood of three normal adult donors, bronchoalveolar lavage cells from one subject, and lung tissue from three patients undergoing lobectomy or pneumonectomy for malignancy, in Western Australia. Targets were five malignant mesothelioma cell lines (JU77, NO36, ONE58, LO68, DeH(m)) plus the control lines K562 and Daudi.
• Exposure: No asbestos or fiber exposure was studied. The experimental exposure was tumour cells incubated with T cell clones in a 4-hour chromium-51 release killing assay, at effector-to-target ratios of 20:1, 10:1, 5:1 and 1:1 for the clones.
• Main results:
  • All clones expressing V gamma 9 were highly cytotoxic to Daudi, even at the lowest ratio tested (1:1), but were ineffective against K562.
  • Clones cytotoxic against K562 generally used a member of the V gamma I subgroup.
  • Each mesothelioma cell line except DeH(m) was highly susceptible to killing by a number of the clones. The authors described DeH(m) as uniformly resistant.
  • The mesothelioma line NO36 was killed by 11 of the 12 clones tested, regardless of V gamma gene usage.
  • JU77 was not susceptible to V gamma 9 clones but was killed by three of the five clones known to use V gamma I subgroup segments.
  • ONE (ONE58) was killed by all three V gamma 9-expressing clones tested and by three of the five V gamma I subgroup clones.
  • No strict correlation was shown between V gamma and V delta gene usage and killing of mesothelioma cells.
  • Killing of mesothelioma lines did not correlate with the clones' production of interferon-gamma, tumour necrosis factor-alpha, interleukin-2 or interleukin-4, nor with their CD8 expression.
  • V gamma 9-bearing clones produced the highest interferon-gamma concentrations. Interleukin-2 and tumour necrosis factor-alpha production was minimal for all gamma delta clones tested.
  • In comparison clones of alpha beta T cells grown the same way, none of 12 CD4+ clones was cytotoxic. At 20:1, 4 of 14 CD8+ clones tested killed JU77 (mean cytotoxicity 21 plus or minus 3%) and 5 of 13 killed NO36 (27 plus or minus 7%). None killed K562 or Daudi.
• The authors' conclusion: The authors concluded that the killing process is influenced by the properties of individual tumour targets, even within a single tissue type, and that properties of the individual T cell clones also influence which targets are killed.
• Limitations the authors state:
  • Fewer data were available on the V gamma 9-bearing clones.
  • The killing assay was repeated (2-3 times) only for the 6 clones with enough cells, and maximum cytotoxicity varied somewhat between experiments.
  • The authors said the relevance of gamma delta T cells to defence against cancer in the body (in vivo) is unknown.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Necrosis.

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