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... Female C57BL/6 (H-2 b ), B6CBAF1/J (H-2 b/k ), and B6.C-H-2 bm1 /ByJ (H2 bm1 ) mice were purchased from The Jackson Laboratory (Bar Harbor, ME). C2 � (H-2 b ) mice, which lack MHC class II molecules =-=(41)-=-, and �MT (H-2 b ) mice, which lack mature B cells (42), were bred under license at St. Jude Children’s Research Hospital (Memphis, TN). All mice were held under specific pathogen-free conditions unti...
Roman R. Ganta, Chuanmin Cheng, Melinda J. Wilkerson, Stephen K. Chapes, Roman R. Ganta, Chuanmin Cheng, Melinda J. Wilkerson, Stephen K. ChapesCitation Context
...ound and has been brother-sister mated for over 20 generations over the last 9 years at KSU. These mice do not express MHCII and lack CD4 � T cells (Fig. 1) due to natural and manipulated mutagenesis =-=(21)-=-. We established that these mice are unable to clear E. chaffeensis after infection (20). (iii) B6.129S6-Cd4 tm1Knw (CD4D) mice. CD4D mice were obtained from the Jackson Laboratory. These mice have a ...
Jonathan Sprent, Charles D. Surh, David Agus, Melissa Hurd, Susan Sutton, William R. Heath \"... The effector functions of CD4 + cells in vivo are presumed to reflect a combination of lymphokine-mediated bystander reactions and direct cytotoxic T lymphocyte activity. To assess the relative importance of these two mechanisms, we studied the effects of transferring small doses of purified unprime ...\" Abstract Cited by 4 (0 self) - Add to MetaCart The effector functions of CD4 + cells in vivo are presumed to reflect a combination of lymphokine-mediated bystander reactions and direct cytotoxic T lymphocyte activity. To assess the relative importance of these two mechanisms, we studied the effects of transferring small doses of purified unprimed CD4 + cells to lightly irradiated (600 cGy) recipients expressing major histocompatibility complex class II (Ia) differences. Within the first week after transfer, the host marrow was rapidly repopulated with hemopoietic cells. Thereafter, however, the donor CD4 + cells caused massive destruction of hemopoietic cells, both in marrow and spleen. Marrow aplasia did not affect stromal cells and was prevented by coinjecting donor but not host bone marrow. The use of allotypic markers and fluorescence-activated cell sorter analysis indicated that the destructive effects of CD4 + cells were directed selectively to host Ia + hemopoietic cells, including stem cells; donor hemopoietic cells and Ia- host T cells were spared. No evidence could be found that the ongoing destruction of host cells impaired the capacity of donor stem cells to repopulate marrow, spleen, or thymus. Moreover, CD4 + cells failed to destroy host-type hemopoietic cells from h-deficient mice. Tissue destruction by CD4 § cells thus did not seem to reflect a bystander reaction. We conclude that, under defined conditions, CD4 + cells can manifest extremely potentCitation Context
...ed from breeding pairs obtained from the National Cancer Institute (Frederick, MD). Ia-deficient mice on the B6 background were kindly provided by Dr. L. Glimcher (Harvard Medical School, Boston, MA) =-=(12)-=-. Irradiation. Mice were exposed to a single dose of y-irradiation (80 cGy/min) by an irradiator (Gammacell 40; Atomic Energy of Canada, Ottawa, Canada). CellPurification. As described elsewhere (13),...
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...ex (MHC) functions (Table 1). C57BL/6 I-A �/� mice are deficient in class II MHC because the targeted disruption of I-A� is set against a mutation in I-E; there are very few CD4 � cells in these mice =-=(7, 19)-=-. � 2m �/� mice are severely deficient in the expression of most conventional class I MHC molecules and nonconventional class Ib MHC molecules; there are very few CD8 � cells in these mice (5, 59). Li...
\"... The majority (�70%) of postselection CD4 � single-positive (SP) thymocytes are CD8 lo CD4 hi. These cells express very low levels of CD8, undetectable by flow cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8 � CD4 hi thymocytes, whi ...\" Abstract Cited by 3 (0 self) - Add to MetaCart The majority (�70%) of postselection CD4 � single-positive (SP) thymocytes are CD8 lo CD4 hi. These cells express very low levels of CD8, undetectable by flow cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8 � CD4 hi thymocytes, which account for the remaining �30 % of the SP CD4 � thymocytes, CD8 lo CD4 hi cells are functionally immature and short-lived unless they receive an unidentified maturation signal from the thymus. In this study, we tested the hypothesis that this signal is provided by a T cell receptor (TCR)–major histocompatibility complex (MHC) class II interaction. Using intrathymic transfer, we show that the immature CD8 lo CD4 hi cells could complete their intrathymic maturation and populate the peripheral lymphoid organs in the absence of MHC class II (and class I) molecules. Furthermore, in mice devoid of class II (and class I) molecules, the progeny of CD8 lo CD4 hi cells was long-lived and functionally reactive to allogeneic class II molecules, although their numbers in the spleen and the mesenteric lymph node were �40–50 % lower than those in class II � mice 5 mo after transfer. Control experiments demonstrated that the surviving cells did not originate from the contaminating mature thymocytes. These results demonstrate that the final maturation, proliferation, and peripheral survivalCitation Context
...Materials and Methods Mice. C57BL/6 (B6) mice and their Ly-5.2 congenic variant (B6.Ly-5.2) were purchased from the National Cancer Institute animal facility (Frederick, MD). Class II–deficient (CII� =-=[16]-=-) mice and class I/II–deficient mice on a B6 background (12th backcross, CI/II� [17]) were purchased from Taconic Farms. The B6 Thy-1 congenic variant strain, B6.PL–thy-1a Cy, as well as the mice gene...
\"... In vitro studies have revealed that help for cytotoxic T lymphocyte (CTL) induction can be mediated through several pathways, including direct recognition of allogeneic class II antigens by CD4 § cells, direct recognition of altogeneic class I antigens by CD4-independent CD8 + cells, an ...\" Abstract Cited by 3 (0 self) - Add to MetaCart In vitro studies have revealed that help for cytotoxic T lymphocyte (CTL) induction can be mediated through several pathways, including direct recognition of allogeneic class II antigens by CD4 § cells, direct recognition of altogeneic class I antigens by quot;CD4-independent quot; CD8 + cells, and quot;indirect quot; recognition of peptides of alloantigens presented in association with self class II molecules. Whereas good evidence for the two direct pathways is available in vivo, there is relatively little evidence to show that indirect recognition can initiate graft rejection. This study examined the role of indirect allorecognition during the generation of CTLs in mice as they rejected major histocompatibility complex (MHC) class II-deficient skin after depletion of CD8 + T cells in vivo. Recipients were depleted of CD8 + T cells by in vivo treatment with anti-CD8 monoclonal antibody and then grafted with allogeneic skin lacking MHC class II antigens. The mice rejected the skin grafts rapidly. Although flow cytometry showed marked depletion of CD8 + T cells in these mice, we found that (a) CD8 + CTLs were generated and sensitized to MHC class I antigens of the donor; (b) the generation of the CD8 + CTLs required the help in vivo of CD4 + cells, as well as priming with the allogeneic skin graft; and (c) the CD4 + T helper cells were sensitized indirectly to donor peptides presented in association with class II antigens on recipientCitation Context
...ice were supplied by the Edwin L. Steele Laboratory at Massachusetts General Hospital (Boston, MA). The generation of [129 x B6]F3 MHC class II knockout mice (H-2b), (II-) has been reported elsewhere =-=(6)-=-. Briefly, the A~ b gene was disrupted in the D3 embryonic stem cell line of 129/Sv origin using the technique of homologous recombination. Cloned embryonic stem ceils expressing the mutant gene were ...
Doi:j. Clin Microbiol, William R. Bishai, Nancy Hooper Jafar H. Razeq, Nancy G. Baruch, Monica J. Lathan, Leonard N. Mukasa, Wendy A. Cronin, Jonathan E. Golub, Laurence S. Magder, Isolates Low CopytuberculosisCitation Context
...mice (Fig. 1B). Similar frequencies of CD8 T cells recognizing TSKB20/Kb and TSKB18/Kb tetramers were observed in B6 and B6129F1/Tac mice (the strain used as the wild-type control for MHC II KO mice =-=[11]-=-) (Fig. 1C). In the only previous report of CD8 T-cell responses to multiple epitopes in the absence of CD4 T-cell help, no differences were observed in the frequencies of CD8 T cells specific for ...
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... for nonMHCII molecules that serve as functional superantigen receptors [16, 17]. These studies used mice that have a functional deletion in the A � gene that disrupts the surface expression of MHCII =-=[18, 19]-=-. We originally bred and maintained these mice in laminar flow isolators with autoclaved cages, bedding, and water under the assumption that these mice were immunologically compromised. However, some ...
\"... Rather unexpectedly, major histocompatibility complex class II-deficient mice have a significant population of peripheral CD4 + T lymphocytes. We have investigated these cells at the population and clonal levels. CD4 + T lymphocytes from class II-deficient animals are thymically derived, appear earl ...\" Abstract Cited by 1 (0 self) - Add to MetaCart Rather unexpectedly, major histocompatibility complex class II-deficient mice have a significant population of peripheral CD4 + T lymphocytes. We have investigated these cells at the population and clonal levels. CD4 + T lymphocytes from class II-deficient animals are thymically derived, appear early in ontogeny, exhibit the phenotype of resting memory cells, are potentially functional by several criteria, and have a diverse T cell receptor repertoire. They do not include substantially elevated numbers of NKI.1 § cells. Hybridomas derived after polyclonal stimulation of the CD4 + lymphocytes from class II-deficient animals include a subset with an unusual reactivity pattern, responding to splenocytes from many mouse strains including the strain of origin. Most members of this subset recognize the major histocompatibllity complex class Ib molecule CD1; their heterogenous reactivities and T cell receptor usage further suggest the involvement of peptides and/or highly variable posttranslational modifications. M ost CD4 + T cells depend on an interaction with the MHC class II molecules expressed on thymic stroma to complete differentiation. As a consequence, mice that \"... The deletion of COOH-terminal Src kinase (Csk), a negative regulator of Src family protein tyrosine kinases (PTKs), in immature thymocytes results in the development of �/ � T lineage cells in T cell receptor (TCR) �-deficient or recombination activating gene (rag)-1–deficient mice. The function of ...\" Abstract Cited by 1 (0 self) - Add to MetaCart The deletion of COOH-terminal Src kinase (Csk), a negative regulator of Src family protein tyrosine kinases (PTKs), in immature thymocytes results in the development of �/ � T lineage cells in T cell receptor (TCR) �-deficient or recombination activating gene (rag)-1–deficient mice. The function of Csk as a repressor of Lck and Fyn activity suggests activation of these PTKs is solely responsible for the phenotype observed in csk-deficient T lineage cells. We provide genetic evidence for this notion as �/ � T cell development is blocked in lck�/�fyn�/ � cskdeficient mice. It remains unclear whether activation of Lck and Fyn in the absence of Csk uncouples �/ � T cell development entirely from engagement of surface-expressed receptors. We show that in mice expressing the �/ � TCR on csk-deficient thymocytes, positive selection is biased towards the CD4 lineage and does not require the presence of major histocompatibility complex (MHC) class I and II. Furthermore, the introduction of an MHC class I–restricted transgenic TCR into a csk-deficient background results in the development of mainly CD4 T cells carrying the transgenic TCR both in selecting and nonselecting MHC background. Thus, TCR–MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of Csk. However, TCR-mediated negative selection of csk-deficient, TCR transgenic cells is normal. These data suggest a differential involvement of the Csk-mediated regulation of Src family PTKs in positive and negative selection of developing thymocytes. Key words: thymocyte development • thymic selection • conditional gene targeting • T cell receptor • Src family kinases>>> 更多资讯详情请访问蚂蚁淘商城
