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The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells.

Tyznik AJ, Sun JC, Bevan MJ - J. Exp. Med. (2004)

Bottom Line: In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II-restricted epitopes in addition to the expected responses to MHC class I-restricted epitopes.Further experiments suggested that these two observations are linked and that the CD8 population in CD4-/- mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus.These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4-/- mice as models of helper deficiency.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.

ABSTRACT
In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II-restricted epitopes in addition to the expected responses to MHC class I-restricted epitopes. A similar response by CD8+ T cells to class II-restricted epitopes was not observed in wild-type mice, or in mice that had been acutely depleted of CD4+ T cells just before the immunization. Coincident with this unexpected response to class II-restricted epitopes, it was also observed that the CD8+ response to the class I-restricted epitopes was consistently lower in CD4-/- mice than in wild-type mice. Further experiments suggested that these two observations are linked and that the CD8 population in CD4-/- mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus. These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4-/- mice as models of helper deficiency.

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C57BL/6 mice acutely depleted of CD4+ cells do not mount a CD8+ T cell response to MHC class II–restricted peptides. C57BL/6 mice were depleted of CD4+ T cells by three injections of anti-CD4 mAb and infected with rLmOva. LLO190–201 and Ova257–264-specific CD4+ or CD8+ T cells were quantified by intracellular IFN-γ staining day 7 after infection and after in vitro stimulation with or without peptide. Numbers represent the percentage of Ag-specific cells in the CD4+ or CD8+ T cell population. This experiment is representative of two mice per group from two independent experiments.
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fig4: C57BL/6 mice acutely depleted of CD4+ cells do not mount a CD8+ T cell response to MHC class II–restricted peptides. C57BL/6 mice were depleted of CD4+ T cells by three injections of anti-CD4 mAb and infected with rLmOva. LLO190–201 and Ova257–264-specific CD4+ or CD8+ T cells were quantified by intracellular IFN-γ staining day 7 after infection and after in vitro stimulation with or without peptide. Numbers represent the percentage of Ag-specific cells in the CD4+ or CD8+ T cell population. This experiment is representative of two mice per group from two independent experiments.

Mentions: We addressed the possibility that class II–specific CD8+ T cells may be present in a normal mouse but are few or undetectable during acute infections due to peripheral competition with CD4+ T cells specific for the same epitope. To address this possibility, wild-type mice were depleted of CD4+ cells in vivo using anti-CD4 mAb just before immunization. As expected, few CD4+ cells were detected in the spleen 7 d after infection with rLmOva in the CD4-depleted mice (Fig. 4, left). The first difference observed in these CD4-depleted mice compared with CD4−/− mice was that the CD8+ T cell response to the H-2Kb–restricted Ova257–264 peptide was similar in both mice (Fig. 4, right). The second observation was that, unlike the CD8 response to LLO190–201 in CD4−/− mice, CD4-depleted mice did not respond to the class II–restricted peptide (Fig. 4, right). It is also noteworthy that the hint of a CD8 response to the class II–restricted peptide observed in normal B6 mice in Figs. 1–4 is not observed in CD4-depleted mice. These findings indicate that the mismatch in coreceptor and MHC recognition is due to abnormal development of the T cells in the CD4−/− mice and not due to peripheral competition for MHC–peptide complexes.


The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells.

Tyznik AJ, Sun JC, Bevan MJ - J. Exp. Med. (2004)

C57BL/6 mice acutely depleted of CD4+ cells do not mount a CD8+ T cell response to MHC class II–restricted peptides. C57BL/6 mice were depleted of CD4+ T cells by three injections of anti-CD4 mAb and infected with rLmOva. LLO190–201 and Ova257–264-specific CD4+ or CD8+ T cells were quantified by intracellular IFN-γ staining day 7 after infection and after in vitro stimulation with or without peptide. Numbers represent the percentage of Ag-specific cells in the CD4+ or CD8+ T cell population. This experiment is representative of two mice per group from two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211827&req=5

fig4: C57BL/6 mice acutely depleted of CD4+ cells do not mount a CD8+ T cell response to MHC class II–restricted peptides. C57BL/6 mice were depleted of CD4+ T cells by three injections of anti-CD4 mAb and infected with rLmOva. LLO190–201 and Ova257–264-specific CD4+ or CD8+ T cells were quantified by intracellular IFN-γ staining day 7 after infection and after in vitro stimulation with or without peptide. Numbers represent the percentage of Ag-specific cells in the CD4+ or CD8+ T cell population. This experiment is representative of two mice per group from two independent experiments.
Mentions: We addressed the possibility that class II–specific CD8+ T cells may be present in a normal mouse but are few or undetectable during acute infections due to peripheral competition with CD4+ T cells specific for the same epitope. To address this possibility, wild-type mice were depleted of CD4+ cells in vivo using anti-CD4 mAb just before immunization. As expected, few CD4+ cells were detected in the spleen 7 d after infection with rLmOva in the CD4-depleted mice (Fig. 4, left). The first difference observed in these CD4-depleted mice compared with CD4−/− mice was that the CD8+ T cell response to the H-2Kb–restricted Ova257–264 peptide was similar in both mice (Fig. 4, right). The second observation was that, unlike the CD8 response to LLO190–201 in CD4−/− mice, CD4-depleted mice did not respond to the class II–restricted peptide (Fig. 4, right). It is also noteworthy that the hint of a CD8 response to the class II–restricted peptide observed in normal B6 mice in Figs. 1–4 is not observed in CD4-depleted mice. These findings indicate that the mismatch in coreceptor and MHC recognition is due to abnormal development of the T cells in the CD4−/− mice and not due to peripheral competition for MHC–peptide complexes.

Bottom Line: In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II-restricted epitopes in addition to the expected responses to MHC class I-restricted epitopes.Further experiments suggested that these two observations are linked and that the CD8 population in CD4-/- mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus.These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4-/- mice as models of helper deficiency.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.

ABSTRACT
In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II-restricted epitopes in addition to the expected responses to MHC class I-restricted epitopes. A similar response by CD8+ T cells to class II-restricted epitopes was not observed in wild-type mice, or in mice that had been acutely depleted of CD4+ T cells just before the immunization. Coincident with this unexpected response to class II-restricted epitopes, it was also observed that the CD8+ response to the class I-restricted epitopes was consistently lower in CD4-/- mice than in wild-type mice. Further experiments suggested that these two observations are linked and that the CD8 population in CD4-/- mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus. These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4-/- mice as models of helper deficiency.

Show MeSH
Related in: MedlinePlus