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Published on: June 22, 2016
Subpopulations of CD4+ cells in lpr/lpr mice: differences in expression of T cell receptor/CD3 complex and
T Asano1, Y Yoshikai, K Matsumoto
1Department of Immunology, Kyushu University, Fukuoka, Japan.
Insights
CD4+ T cells in autoimmune-prone mice show distinct subpopulations. B220-CD4+ cells in these mice are phenotypically and functionally different from normal, impacting immune responses.
Area of Science:
- Immunology
- Autoimmunity
- T cell biology
Background:
- Autoimmune diseases often involve dysregulation of T cell populations.
- C57BL/6 lpr/lpr mice are a model for autoimmune conditions.
- CD4+ T cells can differentiate into distinct subpopulations with varying functions.
Purpose of the Study:
- To investigate the phenotypic and functional characteristics of CD4+ T cell subpopulations in autoimmune-prone C57BL/6 lpr/lpr mice.
- To compare these subpopulations with those from normal C57BL/6 +/+ mice.
- To understand the role of B220 expression in CD4+ T cell function.
Main Methods:
- Flow cytometry was used to analyze cell surface antigens (B220, CD4, CD8, PgP-1, CD3).
- T cell receptor (TcR)/CD3 complex expression was assessed.
- Messenger RNA (mRNA) levels for TcR C alpha, C beta, and V beta 8 were quantified.
- Functional assays, including proliferative response and interleukin-2 (IL-2) production upon anti-CD3 stimulation, were performed.
Main Results:
- Two CD4+ T cell subpopulations, B220-CD4+ and B220+CD4+, were identified in lpr/lpr mice.
- B220+CD4+ and B220+CD4-CD8- cells in lpr/lpr mice showed lower TcR/CD3 expression compared to normal B220-CD4+ cells.
- B220-CD4+ cells in lpr/lpr mice exhibited heterogeneity in PgP-1 and CD3 expression and reduced responsiveness to anti-CD3 stimulation.
- V beta 8 mRNA was preferentially expressed in B220+CD4-CD8- cells from lpr/lpr mice.
Conclusions:
- The B220-CD4+ T cell population in lpr/lpr mice displays distinct phenotypic and functional properties compared to normal mice.
- These differences in T cell subpopulations may contribute to the autoimmune pathology observed in lpr/lpr mice.
- The study highlights the importance of characterizing T cell heterogeneity in autoimmune disease research.
Abstract:
CD4+ cells from autoimmune-prone C57BL/6 lpr/lpr mice contain two subpopulations, B220-CD4+ and B220+CD4+ cells. Highly purified B220-CD4+ cells from C57BL/6 +/+ and lpr/lpr mice were examined by comparing functional characteristics and expression of cell surface antigens and T cell receptor (TcR)/CD3 complex. Both lpr B220+CD4+ and B220+CD4-CD8- cells, most of which were PgP-1 positive, expressed TcR/CD3 complex on the cell surface at lower level as compared with B220-CD4+ cells of age-matched normal mice. In addition, the B2200-CD4+ cells were heterogeneous on the basis of surface expression of PgP-1 and CD3 antigens. Normal levels of TcR C alpha-, C beta- and V beta 8-specific mRNA were found in the B220-CD4+ cells and B220+CD4+ cells as compared with normal B220-CD4+ cells, while V beta 8-specific mRNA was preferentially expressed only by B220+CD4-CD8- cells. Either B220+CD4+ cells and B220+CD4-CD8- cells failed to respond to anti-CD3 monoclonal antibody (MoAb) as assessed by proliferative responses and production of interleukin-2 (IL-2). However, appreciable levels of reactivity to anti-CD3 MoAb were detected in the B220-CD4+ cells, although the responsiveness of this subset to such stimuli were reduced, compared with those of normal control. These results indicate that the B220-CD4+ cells in lpr mice are phenotypically and functionally distinct from normal B220-CD4+ cells.
