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T cell stimulation in vivo by lipopolysaccharide (LPS).

Tough DF, Sun S, Sprent J - J. Exp. Med. (1997)

Bottom Line: As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8(+) T cells, and, at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi)) cells.However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44(hi) subset of CD8(+) cells.In contrast with B cells, proliferative responses of CD44(hi) CD8(+) cells require only very low doses of LPS (10 ng).

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Lipopolysaccharide (LPS) from gram-negative bacteria causes polyclonal activation of B cells and stimulation of macrophages and other APC. We show here that, under in vivo conditions, LPS also induces strong stimulation of T cells. As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8(+) T cells, and, at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi)) cells. However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44(hi) subset of CD8(+) cells. In contrast with B cells, proliferative responses of CD44(hi) CD8(+) cells require only very low doses of LPS (10 ng). Based on studies with LPS-nonresponder and gene-knockout mice, LPS-induced proliferation of CD44(hi) CD8(+) cells appears to operate via an indirect pathway involving LPS stimulation of APC and release of type I (alpha, beta) interferon (IFN-I). Similar selective stimulation of CD44(hi) CD8(+) cells occurs in viral infections and after injection of IFN-I, implying a common mechanism. Hence, intermittent exposure to pathogens (gram-negative bacteria and viruses) could contribute to the high background proliferation of memory-phenotype CD8(+) cells found in normal animals.

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Effect of LPS injection on T and  B cell proliferation in vivo. Graded doses of  LPS were injected intravenously into B6  mice. Mice were immediately given BrdU  in their drinking water, and LN and spleen  cells were analyzed 3 d later. The three leftmost columns show percent BrdU labeling  for CD44hi (□) and CD44lo (○) CD8+ and  CD4+ cells and total B220+ cells (▴), while  the right hand panel shows the percentage  of total CD8+ cells expressing high levels of  Ly-6C (Ly-6Chi). The data represent mean  values from two or three mice per point  (± SD).
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Figure 1: Effect of LPS injection on T and B cell proliferation in vivo. Graded doses of LPS were injected intravenously into B6 mice. Mice were immediately given BrdU in their drinking water, and LN and spleen cells were analyzed 3 d later. The three leftmost columns show percent BrdU labeling for CD44hi (□) and CD44lo (○) CD8+ and CD4+ cells and total B220+ cells (▴), while the right hand panel shows the percentage of total CD8+ cells expressing high levels of Ly-6C (Ly-6Chi). The data represent mean values from two or three mice per point (± SD).

Mentions: As expected, LPS injection caused significant proliferation of B cells, especially in spleen (Fig. 1). However, relative to the background proliferation in uninjected mice, BrdU incorporation by B cells was only seen after injection of relatively high doses of LPS (⩾10 μg). For T cells, LPS injection had minimal effects on CD4+ cells. Thus, even high doses of LPS had no effect on naive (CD44lo) CD4+ cells and caused only a slight increase in the high (30%) background rate of proliferation of memory–phenotype (CD44hi) cells. Quite different results applied to CD8+ cells. As for CD4+ cells, LPS injection did not alter the slow turnover of CD44lo cells. However, even very low doses of LPS (10 ng) caused substantial proliferation of CD44hi CD8+ cells, both in spleen and LN; with higher doses of LPS, BrdU labeling of CD44hi CD8+ cells reached 70% (compared with 20% in uninjected mice). Significantly, LPS injection caused a considerable increase in Ly6C expression on CD8+ cells. Upregulation of Ly6C expression on (total) CD8+ cells is prominent in mice injected with Poly I:C and IFN-I and is reported to be controlled specifically by IFN-I (16). Hence, the upregulation of Ly6C on CD8+ cells after LPS injection signified the production of IFN-I.


T cell stimulation in vivo by lipopolysaccharide (LPS).

Tough DF, Sun S, Sprent J - J. Exp. Med. (1997)

Effect of LPS injection on T and  B cell proliferation in vivo. Graded doses of  LPS were injected intravenously into B6  mice. Mice were immediately given BrdU  in their drinking water, and LN and spleen  cells were analyzed 3 d later. The three leftmost columns show percent BrdU labeling  for CD44hi (□) and CD44lo (○) CD8+ and  CD4+ cells and total B220+ cells (▴), while  the right hand panel shows the percentage  of total CD8+ cells expressing high levels of  Ly-6C (Ly-6Chi). The data represent mean  values from two or three mice per point  (± SD).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196347&req=5

Figure 1: Effect of LPS injection on T and B cell proliferation in vivo. Graded doses of LPS were injected intravenously into B6 mice. Mice were immediately given BrdU in their drinking water, and LN and spleen cells were analyzed 3 d later. The three leftmost columns show percent BrdU labeling for CD44hi (□) and CD44lo (○) CD8+ and CD4+ cells and total B220+ cells (▴), while the right hand panel shows the percentage of total CD8+ cells expressing high levels of Ly-6C (Ly-6Chi). The data represent mean values from two or three mice per point (± SD).
Mentions: As expected, LPS injection caused significant proliferation of B cells, especially in spleen (Fig. 1). However, relative to the background proliferation in uninjected mice, BrdU incorporation by B cells was only seen after injection of relatively high doses of LPS (⩾10 μg). For T cells, LPS injection had minimal effects on CD4+ cells. Thus, even high doses of LPS had no effect on naive (CD44lo) CD4+ cells and caused only a slight increase in the high (30%) background rate of proliferation of memory–phenotype (CD44hi) cells. Quite different results applied to CD8+ cells. As for CD4+ cells, LPS injection did not alter the slow turnover of CD44lo cells. However, even very low doses of LPS (10 ng) caused substantial proliferation of CD44hi CD8+ cells, both in spleen and LN; with higher doses of LPS, BrdU labeling of CD44hi CD8+ cells reached 70% (compared with 20% in uninjected mice). Significantly, LPS injection caused a considerable increase in Ly6C expression on CD8+ cells. Upregulation of Ly6C expression on (total) CD8+ cells is prominent in mice injected with Poly I:C and IFN-I and is reported to be controlled specifically by IFN-I (16). Hence, the upregulation of Ly6C on CD8+ cells after LPS injection signified the production of IFN-I.

Bottom Line: As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8(+) T cells, and, at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi)) cells.However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44(hi) subset of CD8(+) cells.In contrast with B cells, proliferative responses of CD44(hi) CD8(+) cells require only very low doses of LPS (10 ng).

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Lipopolysaccharide (LPS) from gram-negative bacteria causes polyclonal activation of B cells and stimulation of macrophages and other APC. We show here that, under in vivo conditions, LPS also induces strong stimulation of T cells. As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8(+) T cells, and, at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi)) cells. However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44(hi) subset of CD8(+) cells. In contrast with B cells, proliferative responses of CD44(hi) CD8(+) cells require only very low doses of LPS (10 ng). Based on studies with LPS-nonresponder and gene-knockout mice, LPS-induced proliferation of CD44(hi) CD8(+) cells appears to operate via an indirect pathway involving LPS stimulation of APC and release of type I (alpha, beta) interferon (IFN-I). Similar selective stimulation of CD44(hi) CD8(+) cells occurs in viral infections and after injection of IFN-I, implying a common mechanism. Hence, intermittent exposure to pathogens (gram-negative bacteria and viruses) could contribute to the high background proliferation of memory-phenotype CD8(+) cells found in normal animals.

Show MeSH
Related in: MedlinePlus