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Identification and characterization of a unique subpopulation of double negative splenic T cells which express the [alpha beta] T cell receptor Ingram, Andrea
Abstract
A unique class of T lymphocytes has been identified in the spleen of normal mice. This splenic T cell population, which expresses the αβ TCR associated with the CD3 complex yet lacks the CD4 and CD8 coreceptor molecules, constitutes approximately 0.1-0.3% of total nucleated cells and 17- 22% of CD4[sup]- CD8[sup]- HSA[sup]- Mac-1[sup]- cells in the normal murine spleen. Phenotypic analysis of splenic TCR αβ[sup]+ CD4[sup]- CD8[sup]- HSA[sup]- Mac-1[sup]- (DNαβT) cells demonstrated the expression of Lyt-1, Pgp-1, ICAM-1 and the transferrin receptor whereas minimal to no B220 or YE1/19 expression was observed. Amongst splenic DNαβT cells there is a higher frequency of V[sub]β8 usage in comparison with mature SP T cells. Similar to TCR αβ[sup]+ DN thymocytes, splenic DNαβT cells proliferate in the presence of IL-7 and this response is enhanced by the addition of IL-1. CD4[sup]+ and CD8[sup]+ SP T cells, in contrast do not respond to IL-7 alone or in combination with IL-1. Splenic DNαβT cells are considered to be mature based on the expression of the heat stable antigen. Furthermore, this splenic T cell subpopulation expresses a functional T cell receptor as suggested by their responsiveness to crosslinking of the TCR associated CD3 complex which is comparable to that of mature SP T cells. In contrast, splenic TCR γδ[sup]+ DN T cells were nonresponsive to anti-CD3 crosslinking despite the expression of the TCR/CD3 complex. The addition of IL-1, however, appeared to restore the responsiveness of TCR γδ[sup]+ DN towards the activation of the TCR/CD3 complex. The functional maturity of the splenic DNαβT cell population was confirmed by their ability to express cytokine specific mRNA. DNαβT cells constitutively express IFN[sub]γ message whereas IL-4 mRNA was induced by crosslinking of the TCR associated CD3 complex. SP T cells, in contrast, express messages for IFN[sub]γ and IL-4 as well as IL-2 only in response to anti-CD3 crosslinking. The above results support the hypothesis that splenic DNαβT cells represent a unique class of mature T cells which are related to the phenotypically similar cells found in the thymus yet are distinct from the classical type of mature T cell which expresses the SP phenotype.
Item Metadata
Title |
Identification and characterization of a unique subpopulation of double negative splenic T cells which express the [alpha beta] T cell receptor
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1995
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Description |
A unique class of T lymphocytes has been identified in the spleen of normal mice. This splenic T
cell population, which expresses the αβ TCR associated with the CD3 complex yet lacks the CD4
and CD8 coreceptor molecules, constitutes approximately 0.1-0.3% of total nucleated cells and 17-
22% of CD4[sup]- CD8[sup]- HSA[sup]- Mac-1[sup]- cells in the normal murine spleen. Phenotypic analysis of
splenic TCR αβ[sup]+ CD4[sup]- CD8[sup]- HSA[sup]- Mac-1[sup]- (DNαβT) cells demonstrated the expression of Lyt-1,
Pgp-1, ICAM-1 and the transferrin receptor whereas minimal to no B220 or YE1/19 expression
was observed. Amongst splenic DNαβT cells there is a higher frequency of V[sub]β8 usage in
comparison with mature SP T cells. Similar to TCR αβ[sup]+ DN thymocytes, splenic DNαβT cells
proliferate in the presence of IL-7 and this response is enhanced by the addition of IL-1. CD4[sup]+
and CD8[sup]+ SP T cells, in contrast do not respond to IL-7 alone or in combination with IL-1.
Splenic DNαβT cells are considered to be mature based on the expression of the heat stable
antigen. Furthermore, this splenic T cell subpopulation expresses a functional T cell receptor as
suggested by their responsiveness to crosslinking of the TCR associated CD3 complex which is
comparable to that of mature SP T cells. In contrast, splenic TCR γδ[sup]+ DN T cells were
nonresponsive to anti-CD3 crosslinking despite the expression of the TCR/CD3 complex. The
addition of IL-1, however, appeared to restore the responsiveness of TCR γδ[sup]+ DN towards the
activation of the TCR/CD3 complex. The functional maturity of the splenic DNαβT cell
population was confirmed by their ability to express cytokine specific mRNA. DNαβT cells
constitutively express IFN[sub]γ message whereas IL-4 mRNA was induced by crosslinking of the TCR
associated CD3 complex. SP T cells, in contrast, express messages for IFN[sub]γ and IL-4 as well as
IL-2 only in response to anti-CD3 crosslinking. The above results support the hypothesis that
splenic DNαβT cells represent a unique class of mature T cells which are related to the
phenotypically similar cells found in the thymus yet are distinct from the classical type of mature T
cell which expresses the SP phenotype.
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Extent |
8285168 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-01-21
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0087005
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1995-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.