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The expression of CD45RB on antigen-responsive CD4+ lymphocytes: mouse strain polymorphism and different responses to
L C Gahring1, D N Ernst, C G Romball
1Scripps Research Institute, Department of Immunology, La Jolla, California 92037.
Insights
CD45RB expression on CD4+ T cells varies between mouse strains and antigens. This study reveals strain-specific responses to HGG and antigen-dependent shifts in CD45RB expression, impacting T cell proliferation and cytokine production.
Area of Science:
- Immunology
- Cellular Immunology
- T cell biology
Background:
- CD45RB is a marker used to distinguish T cell subsets with different functional properties.
- Previous studies suggest a role for CD45RB expression in regulating T cell activation and differentiation.
- Understanding T cell heterogeneity is crucial for developing effective immunotherapies.
Purpose of the Study:
- To investigate the role of CD45RB expression on CD4+ T cells in response to high-grade glioma (HGG) antigen in different mouse strains.
- To determine if CD45RB expression patterns are consistent across different antigens and mouse strains.
- To analyze the functional consequences of CD45RB heterogeneity on T cell proliferation and cytokine production.
Main Methods:
- Analysis of CD45RB expression levels on CD4+ T cells from HGG-primed CBA/CaJ and C57BL/6J mice.
- Cell sorting of CD45RBhi and CD45RBlo populations for in vitro culture with HGG and antigen-presenting cells.
- Assessment of T cell proliferation and IL-2/IL-4 production.
- Comparison of responses to HGG and keyhole limpet hemocyanin (KLH) antigens.
Main Results:
- CD45RBlo CD4+ T cells predominated the proliferative response to HGG in CBA/CaJ mice, while CD45RBhi cells were dominant in C57BL/6J mice early after priming.
- Both CD45RBhi and CD45RBlo CD4+ T cells expressed high levels of CD44, indicating activation.
- CD45RBhi cells produced significant IL-2 in response to HGG, whereas CD45RBlo cells did not produce detectable IL-2 or IL-4.
- Responses to KLH showed a different pattern, with an early even distribution and later shift to CD45RBlo cells in C57BL/6J mice.
Conclusions:
- CD45RB expression patterns on primed CD4+ T cells exhibit mouse strain polymorphism.
- Antigen specificity influences the dynamics of CD45RB expression on responding T cells.
- CD45RBhi and CD45RBlo subsets possess distinct functional capabilities regarding proliferation and cytokine production.
Abstract:
The levels of CD45RB expression by HGG-specific CD4+ cells residing in the Ag-draining lymph nodes of HGG-primed CBA/CaJ mice were analyzed. When sorted populations of CD4+, CD45RBhi, and CD4+, CD45RBlo cells were cultured with HGG and Ag-presenting cells, the majority of the proliferative response was found in the CD45RBlo fraction early after in vivo priming (Day 6), and this pattern remained stable through 12 days postpriming. To determine whether this segregation of responsiveness was consistent in other mouse strains, HGG-primed C57BL/6J mice were similarly analyzed. In contrast to findings with the CBA/CaJ strain, the CD4+, CD45RBhi cell fraction obtained from C57BL/6J mice was the predominant responding population early after in vivo priming (Day 6); however, there was a parallel increase in responsiveness of CD4+, CD45RBhi, and CD4+, CD45RBlo cells by Day 12. Thus, there was not a decrease in CD45RBhi expression with a concommitant increase in CD45RBlo expression in CD4+ cells proliferating to HGG. Despite the heterogeneity in CD45RB expression by the primed CD4+ cells of the two strains, the entire proliferative response to HGG early after priming resided in the fraction bearing high levels of membrane CD44, thus arguing for the existence of CD45RBhi, CD44hi and CD45RBlo, CD44hi cells during the early phase of the response. In both mouse strains the CD4+, CD45RBhi subset of primed lymph node cells produced significant levels of IL-2 in response to HGG and APC, whereas no significant IL-2 or IL-4 production was detectable in HGG-stimulated CD45RBlo cells of either strain. The CD4+, CD45RBhi subset also proliferated more vigorously in response to polyclonal activation than the CD4+ CD45RBlo fraction. To examine whether the patterns of CD45RB expression on HGG-primed cells from C57BL/6J mice were common to other antigens, the response profiles were examined after in vivo priming with a second antigen, KLH. In contrast to studies with HGG as the Ag, the proliferative response to KLH in C57BL/6J mice was evenly divided among the CD45RBhi and CD45RBlo fractions on Day 8 after priming, but shifted markedly to the CD45RBlo fraction by Day 12 after priming. Taken together, these data show that the patterns of CD45RB expression on primed populations of CD4+ cells can exhibit mouse strain polymorphism and can differ depending on the choice of antigen for immunization.