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Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.

You-Ten KE, Muise ES, Itié A, Michaliszyn E, Wagner J, Jothy S, Lapp WS, Tremblay ML - J. Exp. Med. (1997)

Bottom Line: However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected.BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency.This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.

ABSTRACT
The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

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Immune function of TC-PTP–deficient mice. (A) Proliferative responses of splenic cells to B- and T cell–specific mitogens, LPS, and  Con A, respectively. Mice were killed 21 d after birth. Data are presented  as the mean ± SE of 3–6 mice/group. (B) Response of splenic PFCs  against SRBCs. Mice of 21 d of age were injected intravenously with  SRBCs and killed 4 d after immunization. Data are presented as the mean  PFC ± SE/106 spleen cells.
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Figure 3: Immune function of TC-PTP–deficient mice. (A) Proliferative responses of splenic cells to B- and T cell–specific mitogens, LPS, and Con A, respectively. Mice were killed 21 d after birth. Data are presented as the mean ± SE of 3–6 mice/group. (B) Response of splenic PFCs against SRBCs. Mice of 21 d of age were injected intravenously with SRBCs and killed 4 d after immunization. Data are presented as the mean PFC ± SE/106 spleen cells.

Mentions: Since we observed thymic atrophy and detected a defective B cell population in the marrow, we investigated T and B cell function 21 d after birth. Splenic cells obtained from TC-PTP −/− mice responded poorly to both T and B cell mitogens, Con A, and LPS, respectively (Fig. 3 A). In addition, in vivo splenic antibody response to SRBCs was suppressed in the TC-PTP −/− animals (Fig. 3 B). Thus, the disruption of the TC-PTP gene led to impaired T and B cell functions, suggesting that TC-PTP is important for the development of immunocompetence of T and B lymphocytes.


Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.

You-Ten KE, Muise ES, Itié A, Michaliszyn E, Wagner J, Jothy S, Lapp WS, Tremblay ML - J. Exp. Med. (1997)

Immune function of TC-PTP–deficient mice. (A) Proliferative responses of splenic cells to B- and T cell–specific mitogens, LPS, and  Con A, respectively. Mice were killed 21 d after birth. Data are presented  as the mean ± SE of 3–6 mice/group. (B) Response of splenic PFCs  against SRBCs. Mice of 21 d of age were injected intravenously with  SRBCs and killed 4 d after immunization. Data are presented as the mean  PFC ± SE/106 spleen cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199020&req=5

Figure 3: Immune function of TC-PTP–deficient mice. (A) Proliferative responses of splenic cells to B- and T cell–specific mitogens, LPS, and Con A, respectively. Mice were killed 21 d after birth. Data are presented as the mean ± SE of 3–6 mice/group. (B) Response of splenic PFCs against SRBCs. Mice of 21 d of age were injected intravenously with SRBCs and killed 4 d after immunization. Data are presented as the mean PFC ± SE/106 spleen cells.
Mentions: Since we observed thymic atrophy and detected a defective B cell population in the marrow, we investigated T and B cell function 21 d after birth. Splenic cells obtained from TC-PTP −/− mice responded poorly to both T and B cell mitogens, Con A, and LPS, respectively (Fig. 3 A). In addition, in vivo splenic antibody response to SRBCs was suppressed in the TC-PTP −/− animals (Fig. 3 B). Thus, the disruption of the TC-PTP gene led to impaired T and B cell functions, suggesting that TC-PTP is important for the development of immunocompetence of T and B lymphocytes.

Bottom Line: However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected.BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency.This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.

ABSTRACT
The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

Show MeSH
Related in: MedlinePlus