Role of CD4+ and CD8+ T cells in the prevention of measles virus-induced encephalitis in mice

Depending on their major histocompatibility complex (MHC) haplotype, inbred mouse strains are either resistant (H2-d, BALB/c), susceptible (H2-k, C3H) or partially resistant (H2-d×k, BaCF1) to intracerebral infection with the neurotropic rodent-adapted measles virus (MV) strain CAM/RBH. Here, mortality is demonstrated to be correlated directly with virus spread and virus replication in the CNS and to be inversely correlated with the activation of MV-specific T cells. Previously, it has been shown that primary CD4+ T cells alone are protective in the resistant background. In the susceptible background, CD4+ T cells acquire protective capacity after immunization with a newly defined CD4+ T cell epitope peptide. In the partially resistant mice, CD4+ T cells provide help for CD8+ T cells and protect in cooperation with them. It seems that the lytic capacity of CD8+ T cells is crucial in providing protection, as MV-specific Ld-restricted CD8+ T cells, which are highly lytic in vitro after transfer, protect naive animals against MV-induced encephalitis (MVE). In contrast, Kk-restricted CD8+ T cells with low lytic capacity do not protect. In the MVE model, CD4+ T cells are able to protect either alone (resistant mice), through cooperation with CD8+ T cells (intermediate susceptible) or after immunization as secondary T cells (susceptible mice). CD8+ T cells are able to protect alone after immunization if they are cytolytic. Thus, susceptibility and resistance depend upon the functional composition of CD4+ and CD8+ T cells governed by the MHC haplotype.

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Role of Genetic Resistance in Invasive Pneumococcal Infection: Identification and Study of Susceptibility and Resistance in Inbred Mouse Strains

Infection and Immunity ◽

10.1128/iai.69.1.426-434.2001 ◽

2001 ◽

Vol 69 (1) ◽

pp. 426-434 ◽

Cited By ~ 90

Author(s):

Neill A. Gingles ◽

Janet E. Alexander ◽

Aras Kadioglu ◽

Peter W. Andrew ◽

Alison Kerr ◽

...

Keyword(s):

Inbred Mice ◽

Inbred Mouse ◽

Genetic Resistance ◽

Pneumococcal Infection ◽

Mouse Strains ◽

Inflammatory Lesions ◽

Invasive Pneumococcal Infection ◽

Susceptibility And Resistance

ABSTRACT From a panel of nine inbred mice strains intranasally infected withStreptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.

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Immunosuppressive factor(s) specific for L-glutamic acid(50)-L- tyrosine(50) (GT). II. Presence of I-J determinants on the GT-suppressive factor

Journal of Experimental Medicine ◽

10.1084/jem.146.1.287 ◽

1977 ◽

Vol 146 (1) ◽

pp. 287-292 ◽

Cited By ~ 52

Author(s):

J Theze ◽

C Waltenbaugh ◽

ME Dorf ◽

B Benacerraf

Keyword(s):

T Cells ◽

Glutamic Acid ◽

Inbred Mouse ◽

Inbred Mouse Strain ◽

Antibody Responses ◽

Mouse Strains ◽

Suppressor T Cells ◽

Suppressor Factor

The responses to the synthetic antigens, L-glutamic acid(60)-L- alanine(30)-L-tyrosine(10) (GAT) and L-glutamic acid(50)-L-tyrosine(50) (GT) are controlled by genes in the I region of the mouse H-2 complex (1-3). Preimmunization of the mice bearing the H-2(p,q,s) nonresponder haplotypes with GAT stimulates the development of suppressor T cells that inhibit in vivo or in vitro antibody responses to GAT complexed to the immunogenic carrier, methylated bovine serum albumin (GAT-MBSA) (4). The copolymer GT is not immunogenic in any inbred mouse strain tested, and has a suppressive effect on the antibody responses to GT-MBSA in mouse strains bearing the H-2(d,f,k,s) haplotypes; suppressor T cells have been demonstrated to be responsible for specific GT suppression (3). We have obtained specific suppressive extracts from thymus and spleen cells of GAT-or GT-primed suppressor strains (5,6). The specific suppressive T-cell factors in the active extracts have been characterized (6,7) and appear similar to the carrier-specific suppressor factor described by Tada and Taniguchi (8). These products belong to a family of newly identified molecules coded for by the I region of the H-2 complex with affinity for antigen and helper (9,10) or suppressive (5-8) regulatory activity on the immune response. Recently, Tada et al. have reported that the keyhole limpet hemocyanin (KLH)-specific suppressor factor is coded for by the I-J subregion of the H-2 complex (11). We now demonstrate also that a GT-specific suppressor factor extracted from the spleens and thymuses of B10.BR (H-2(k)) mice bears determinants controlled by the I-J subregion of the H-2 complex.

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Animal models of Graves' disease

Acta Endocrinologica ◽

10.1530/eje.0.1420001 ◽

2000 ◽

pp. 1-8 ◽

Cited By ~ 29

Author(s):

M Ludgate

Keyword(s):

T Cells ◽

Mhc Class Ii ◽

Inbred Mice ◽

Inbred Mouse ◽

Nod Mice ◽

Autoimmune Response ◽

Mouse Strains ◽

Graves Disease ◽

Genetic Immunisation

Graves' disease (GD) is an autoimmune condition in which goitre and hyperthyroidism are induced by thyroid stimulating antibodies (TSAB) which mimic the action of thyrotrophin (TSH). The target of the autoimmune response is the thyrotrophin receptor (TSHR) and, since its cloning, a number of differing approaches have been adopted in an attempt to develop an animal model of GD. Methods in which synthetic peptides or fragments of the receptor produced in bacteria or insect cells have been injected into animals together with immunological adjuvants have had only limited success in inducing some of the signs and symptoms of GD. Genetic immunisation resulted in thyroiditis in the majority, but TSAB formation in only a minority, of treated inbred mice. Transfer of receptor in vitro primed T cells to syngeneic naive recipients, with priming either using a bacterial fusion protein or genetic immunisation, induced destructive thyroiditis in non-obese diabetic (NOD) mice but lymphocytic thyroiditis in BALBc mice. Furthermore, the orbits of 17/22 of the BALBc animals, but not the NOD animals, with thyroiditis had orbital changes similar to those seen in thyroid eye disease. TSAB and elevated thyroxine levels were induced in AKR/N mice injected with fibroblasts expressing the full length human TSHR and murine major histocompatibility complex (MHC) class II homologous to the recipient mice. No thyroiditis was induced but preliminary results from a different group using the same protocol suggest that receptor autoantibodies and thyroid dysfunction could be transferred using T cells primed in vitro with the receptor and MHC-II expressing cells. The majority of the studies described above have studied inbred mouse strains. In a novel departure, the NMR outbred strain has been treated by genetic immunisation with very promising results, including the induction of increased thyroxine levels in 4/30 female mice, accompanied by TSAB in addition to thyroiditis, and with signs of hyperactivity and orbital pathology. This review discusses the various protocols together with the information regarding the pathogenesis of GD which each has contributed, and concludes with an evaluation of how close we are to mimicking this polygenic, multifactorial disease.

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Role of Inflammatory Mediators in Resistance and Susceptibility to Pneumococcal Infection

Infection and Immunity ◽

10.1128/iai.70.3.1547-1557.2002 ◽

2002 ◽

Vol 70 (3) ◽

pp. 1547-1557 ◽

Cited By ~ 81

Author(s):

Alison R. Kerr ◽

June J. Irvine ◽

Jennifer J. Search ◽

Neill A. Gingles ◽

Aras Kadioglu ◽

...

Keyword(s):

Core Body Temperature ◽

Inbred Mouse ◽

Pneumococcal Infection ◽

Mouse Strains ◽

Isolated Lung ◽

Cytokine Tumor Necrosis Factor ◽

Core Body ◽

Necrosis Factor

ABSTRACT Variations in the host response during pneumonia caused by Streptococcus pneumoniae in susceptible (CBA/Ca) and resistant (BALB/c) inbred mouse strains were investigated. Significant differences were detected in survival time, core body temperature, lung-associated and systemic bacterial loads, mast cell numbers, magnitude and location of cytokine production, lung disruption, and ability of isolated lung cells to release the cytokine tumor necrosis factor (TNF) alpha in vitro. Overall, the results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.

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Regulation of immune responses by I-J gene products. VI. Recognition of I-E molecules by I-J-bearing suppressor factors.

Journal of Experimental Medicine ◽

10.1084/jem.163.4.797 ◽

1986 ◽

Vol 163 (4) ◽

pp. 797-811 ◽

Cited By ~ 10

Author(s):

C Waltenbaugh ◽

L Sun ◽

H Y Lei

Keyword(s):

T Cells ◽

Immune Responses ◽

Inbred Mouse ◽

Mouse Strains ◽

Gene Products ◽

Suppressor T Cells ◽

Primary Target ◽

Suppressor Factor ◽

B Lymphoma Cells

Poly(Glu50Tyr50) (GT) is not immunogenic in most inbred mouse strains. GT injection produces an I-J--bearing, GT-specific T-cell--derived suppressor factor (GT-TsF1) in H-2b,d,k haplotype mice. GT-TsF1 generates second-order suppressor T cells (Ts2) in H-2a,d,k haplotype mice. Here, we show that in order for GT-TsF1 to act, the recipient strain must express I-E molecules. This suggests that T cells are not the primary target of GT-TsF1. GT-TsF1 can be presented by Ia+ A20-2J B lymphoma cells. GT-TsF1 presentation is blocked by anti-I-E, but not by anti--I-A, mAb, whereas GAT presentation is blocked by anti-I-A, but not by anti--I-E, mAbs. These data suggest that I-J recognizes (or is recognized by) I-E. The existence and role of I-J molecules in immune regulation are discussed in light of these data.

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1097 Role of PD-L1 in In-vitro Interaction Between T-cells and Ovarian Tumour Cells

European Journal of Cancer ◽

10.1016/s0959-8049(12)71702-1 ◽

2012 ◽

Vol 48 ◽

pp. S264

Author(s):

J. Chatterjee ◽

N. Haslinda Abdul Aziz ◽

C. Maine ◽

C. Hayford ◽

L. Whilding ◽

...

Keyword(s):

T Cells ◽

Ovarian Tumour ◽

Tumour Cells ◽

In Vitro Interaction

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Memory T cells are anergic to the superantigen staphylococcal enterotoxin B.

Journal of Experimental Medicine ◽

10.1084/jem.176.2.575 ◽

1992 ◽

Vol 176 (2) ◽

pp. 575-579 ◽

Cited By ~ 62

Author(s):

W T Lee ◽

E S Vitetta

Keyword(s):

T Cells ◽

Memory T Cells ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Staphylococcal Enterotoxin ◽

Peripheral Tolerance ◽

Staphylococcal Enterotoxin B ◽

Enterotoxin B

We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome.

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Frequencies of IFNγ- and IL-4-producing cells during Mycobacterium bovis BCG infection in two genetically susceptible mouse strains: role of αβ T cells and NK1.1 cells

Immunology Letters ◽

10.1016/0165-2478(95)00009-t ◽

1995 ◽

Vol 46 (1-2) ◽

pp. 15-19 ◽

Cited By ~ 11

Author(s):

Henrique C. Teixeira ◽

Martin E. Munk ◽

Stefan H.E. Kaufmann

Keyword(s):

T Cells ◽

Mycobacterium Bovis ◽

Mouse Strains ◽

Susceptible Mouse ◽

Mycobacterium Bovis Bcg ◽

Αβ T Cells

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In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

Infection and Immunity ◽

10.1128/iai.00317-06 ◽

2006 ◽

Vol 74 (7) ◽

pp. 3817-3824 ◽

Cited By ~ 58

Author(s):

Karen L. Wozniak ◽

Jatin M. Vyas ◽

Stuart M. Levitz

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell Activation ◽

Cell Activation ◽

Ex Vivo ◽

Interleukin 2 ◽

Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

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