T lymphocyte recognition of human group 1 CD1 molecules: Implications for innate and acquired immunity

2000 ◽  
Vol 12 (6) ◽  
pp. 511-516 ◽  
Author(s):  
Masahiko Sugita ◽  
Michael B Brenner
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Isamu Matsunaga ◽  
Masahiko Sugita

Mycobacterium tuberculosisand related mycobacteria species are unique in that the acid-fast bacilli possess a highly lipid-rich cell wall that not simply confers resistance to treatment with acid alcohol, but also controls their survival and virulence. It has recently been established that a fraction of the cell wall lipid components of mycobacteria can function as antigens targeted by the acquired immunity of the host. Human group 1 CD1 molecules (CD1a, CD1b, and CD1c) bind a pool of lipid antigens expressed by mycobacteria and present them to specific T cells, thereby mediating an effective pathway for host defense against tuberculosis. The contrasting and mutually complementary functions of CD1a and CD1b molecules in terms of the repertoire of antigens they bind have been well appreciated, but it remains to be established how CD1c may play a unique role. Nevertheless, recent advances in our understanding of the CD1c structure as well as the biosynthetic pathway of a CD1c-presented antigen, mannose-1, β-phosphomycoketide, expressed by pathogenic mycobacteria now unravel a new aspect of the group 1 CD1 biology that has not been appreciated in previous studies of CD1a and CD1b molecules.


Immunity ◽  
2017 ◽  
Vol 46 (5) ◽  
pp. 758-759 ◽  
Author(s):  
Florence Roan ◽  
Steven F. Ziegler

Author(s):  
M. Sh. Khubutiya ◽  
E. A. Tarabrin ◽  
E. I. Pervakova ◽  
V. P. Nikulina ◽  
M. A. Godkov

Background. The diseases leading to the need for lung transplantation include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1-antitrypsin deficiency, idiopathic pulmonary hypertension, histiocytosis X, and sarcoidosis. Primary lung transplant dysfunction is a frequent complication after transplantation and represents a multifactorial injury of the transplanted lung, its pathogenesis being associated with a severe hypoxemia of the lung transplant and diffused damage to the alveoli. The clinical presentation is in many ways similar to an acute respiratory distress syndrome, which pathogenesis is primarily effected by the activation of immune system cells. The cytokine production by immunocompetent cells, the synthesis of reactive oxygen and nitrous oxide, being the mediators of inflammation, trigger inflammatory processes in the lungs; the immunoglobulin synthesis derangements also lead to the development of inflammatory abnormalities in the lungs and a poor transplantation outcome.The objective was to study the immunological response in the lung transplant recipients suffering from the underlying disease of various etiology and to determine the immunological predictors of adverse outcome in the early period after bilateral lung transplantation.Material and methods. Twenty nine patients were examined within 2 weeks after lung transplantation: Group 1 comprised 10 patients with cystic fibrosis (6 women, 4 men) aged 27.8 ± 2.7 years; Group 2 included 19 patients (7 women, 12 men) at the age of 38.5 ± 10.4 years having other lung diseases. Mortality was 10% (1 patient) in Group 1, and 52.5% (10 patients) in Group 2. The patients were followed-up according to the standard protocol of postoperative treatment and immunosuppression therapy shemes. Immunological monitoring included the lymphocyte phenotyping, and the assessment of phagocytic activity of neutrophils, the HCT-test, the blood levels of immunoglobulins (Ig) A, M, G, circulating immune complexes, and C-reactive protein. Statistical significance was assessed at p <0.05.Results. On day 5, the T-lymphocyte count in patients of Group 1 was 674 cells/μL (Me), which was 26.7% lower than lower limit of the reference range, but 2.5 times higher than that in patients of Group 2 (266 cells/μL). The number of T-lymphocytes in patients of the 2nd group was recorded at 71.1% below the lower limit of the reference interval (p < 0.05). The blood level of IgA (Me) in patients of Group 1 was within the normal range (Ме– 1.9 g/L), the blood level of IgA (Me) in patients of Group 2 was 1.4 g/L, which was 26.3% lower than below the lower limit of the reference values and lower than in Group 1 (p < 0.05).By day 13, the count of T-lymphocytes in Group 1 had increased 2.2 times compared to day 5, reaching the reference values (Me), and made 1479 cells/μL. In the 2nd group, there was a 1.5-fold increase in T-lymphocyte count (Me 408 cells/μL), which was 3.7 times lower than the lower limit of the reference range and lower than in the 1st group (p < 0.05). The level of IgA in patients of the 1st group increased by 20.8% and amounted to 2.4 g/L (Me), and in patients of the 2nd group, the level of IgA for 2 weeks remained almost unchanged (Me 1.5 g/L ) and was 1.7 times lower than in the 1st group (p < 0.05).Conclusions. On day 5 after transplantation, the patients with cystic fibrosis demonstrated the increase in the T-lymphocyte count and IgA level by 2.5 and 1.4 times, respectively, compared to the patients with other lung diseases. By the end of week 2, T-lymphocyte and IgA values in patients with cystic fibrosis, unlike patients with other lung diseases, had reached the reference range. The T-lymphocyte count and the concentration of IgA below the reference range in the first 2 weeks after lung transplantation were the immunological predictors of adverse outcome.


2009 ◽  
Vol 206 (11) ◽  
pp. 2497-2509 ◽  
Author(s):  
Kyrie Felio ◽  
Hanh Nguyen ◽  
Christopher C. Dascher ◽  
Hak-Jong Choi ◽  
Sha Li ◽  
...  

Group 1 CD1 (CD1a, CD1b, and CD1c)–restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)–infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1–restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1–restricted Mtb lipid–specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1–restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1–restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.


2011 ◽  
Vol 85 (22) ◽  
pp. 11846-11854 ◽  
Author(s):  
E. Battivelli ◽  
J. Migraine ◽  
D. Lecossier ◽  
P. Yeni ◽  
F. Clavel ◽  
...  

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jie Zhao ◽  
Sarah Siddiqui ◽  
Shaobin Shang ◽  
Yao Bian ◽  
Sreya Bagchi ◽  
...  

Group 1 CD1 molecules, CD1a, CD1b and CD1c, present lipid antigens from Mycobacterium tuberculosis (Mtb) to T cells. Mtb lipid-specific group 1 CD1-restricted T cells have been detected in Mtb-infected individuals. However, their role in protective immunity against Mtb remains unclear due to the absence of group 1 CD1 expression in mice. To overcome the challenge, we generated mice that expressed human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, mycolic-acid specific TCR (DN1Tg). Using DN1Tg/hCD1Tg mice, we found that activation of DN1 T cells was initiated in the mediastinal lymph nodes and showed faster kinetics compared to Mtb Ag85B-specific CD4+ T cells after aerosol infection with Mtb. Additionally, activated DN1 T cells exhibited polyfunctional characteristics, accumulated in lung granulomas, and protected against Mtb infection. Therefore, our findings highlight the vaccination potential of targeting group 1 CD1-restricted lipid-specific T cells against Mtb infection.


1996 ◽  
Vol 35 (6) ◽  
pp. A17
Author(s):  
A.E. Kingston ◽  
R. Tomlinson ◽  
B.P. Clark ◽  
J. Harris ◽  
J. Goldsworthy ◽  
...  

Author(s):  
Mai M. Said ◽  
Ramesh K. Nayak ◽  
Randall E. McCoy

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.


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