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Human T lymphocytes expressing gamma/delta T cell antigen receptor
L Moretta1, E Ciccone, M C Mingari
1Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Clinical Immunology and Immunopathology
|January 1, 1989
Summary
This study identifies distinct subsets of T-cell receptor gamma/delta (TCR γ/δ) cells, highlighting their unique characteristics and distribution in peripheral blood and thymus. These findings advance our understanding of immune cell diversity and function.
Area of Science:
- Immunology
- Cell Biology
Background:
- Most T lymphocytes use T-cell receptor alpha/beta (TCR α/β) chains.
- A minor subset of T lymphocytes expresses TCR gamma/delta (TCR γ/δ) heterodimers.
- TCR γ/δ+ cells exhibit distinct phenotypic and functional properties compared to conventional T cells.
Purpose of the Study:
- To characterize the phenotypic and functional differences of TCR γ/δ+ cells.
- To investigate the antigen recognition capabilities of TCR γ/δ+ cells.
- To identify and differentiate subsets of TCR γ/δ+ cells based on their expressed molecules.
Main Methods:
- Enrichment of TCR γ/δ+ cells using monoclonal antibodies and complement targeting CD4 and CD8 antigens.
- Cloning of CD4-8- peripheral blood lymphocytes under limiting dilution conditions.
- Functional assays including mixed lymphocyte culture (MLC), cytotoxicity assays, and analysis of intracellular Ca2+ and lymphokine production.
- Characterization of TCR γ/δ+ subsets using monoclonal antibodies (mAbs) BB3 and delta-TCS-1.
Main Results:
- Cloned CD4-8- lymphocytes were predominantly cytolytic, effectively lysing tumor target cells.
- TCR γ/δ+ cells demonstrated antigen recognition, proliferating in response to allogeneic cells and specifically lysing PHA-induced blast cells.
- Two distinct TCR γ/δ+ subsets were identified: BB3-reactive (Cγ1-encoded, disulfide-linked) and delta-TCS-1 reactive (Cγ2-encoded, nondisulfide-linked).
- BB3 and delta-TCS-1 mAbs induced activation of corresponding cloned cells.
- A subset of delta-TCS-1+ clones expressed CD8 and a specific 55 kDa gamma chain.
- Cγ1-encoded TCR γ/δ+ cells were prevalent in peripheral blood but rare in the thymus.
- Cγ2-encoded TCR γ/δ+ cells were less frequent in peripheral blood but predominated in the thymus.
Conclusions:
- TCR γ/δ+ cells are a distinct population of cytolytic lymphocytes capable of antigen recognition.
- Distinct TCR γ/δ+ subsets, defined by Cγ1 and Cγ2 isotypes, exhibit differential distribution in peripheral blood and thymus.
- These findings reveal significant differences in TCR γ/δ+ subset distribution between the thymus and peripheral blood, with implications for immune surveillance and development.