摘要:

SummaryThe recent description of a selective human CD3γ deficiency and other T‐cell receptor (TCR)/CD3 structural and functional defects, together with previous biochemical data on the structure and interactions of the TCR/CD3 complex, may aid in elucidating the physiology of this multi‐subunit membrane ensemble. CD3γ seemed to be required for the commitment and thymic maturation of an important fraction of T lymphocytes to the CD8 (but not CD4) lineage, perhaps by participating with the CD8 co‐receptor in the instructive signal delivered throtigh the αβ TCR during intrathymic positive selection by HLA class I molecules. The homologous CD3δ component would, in contrast, be necessary for the selection of CD4 lymphocytes by HLA class II molecules. The interaction of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be asymmetrical, taking place through CD3δ and γ respectively. Also, the existence of in vivo functional TCR/CD3 hemireceptors (lacking either CD3γ or CD3δ is suggested, and defects in their relative amount on the T‐cell surface may disrupt unresponsiveness to self antigens and gener

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02950.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Mice from four different inbred strains were infected with liveMycobacterium tuberculosisand the immune response to M. tuberculosis was followed for 24 weeks, using Western blotting. Nearly all mice, irrespective of H‐2 type, reacted with the 3S‐kDa protein band. Antibodies against this secreted 38‐kDa protein were ihe first to appear, 4 weeks after infection. Thereafter the secreted 19‐kDa protein and non‐secreted antigens, such as the 65‐kDa and 33‐kDa proteins, were recognized. The immune response against the non‐secreted antigens was influenced by the mouse strain. However, the 33‐kDa protein band was recognized by all mouse strains after a second injection wilh live M. tuberculosis.The specificity of the antibodies was analysed in Western blot using sonicates ofM. tuberculosis, M. kansasii, M avium. M. terrae, M. gordonae and Escherichia coli. Antibodies against the 38‐kDa and 33‐kDa protein bands seemed to be specific for M. tuberculosis, while antibodies against the 19‐kDa protein band showed limited cross‐reactivity. Antibodies against the 65‐kDa prolein were strongly cross‐reactive.These results suggest that the 38‐kDa protein is secreted in vivo and, therefore, may be available to the humoral immune system at an early stage of infection. The non‐secreted 33‐kDa protein is only recognized by all mouse strains afler pro

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02951.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Human monocytes and macrophages express an isoform of IgG Fe receptor II (FcγRII), FcγRII. Two allotypic variants of this receptor could be distinguished with respect to their ability to bind murine (m)IgG1 complexes either strongly or weakly, defined as high‐responder (HR) and low‐responder (LR). respectively. We investigated the effect of recombinant (r)IFN‐γ on the ability of freshly isolated monocytes, and those cultured for 40 h and 9 days, to mediate antibody‐dependent cell‐mediated cytotoxicity (ADCC), Using human erythrocytes (E) sensitized with mlgGl as target cells, FcγRII was studied selectively. Cells which had been cultured for 40 h exhibit a significantly decreased FcγRII expression, and FcγRll‐mediated ADCC activity as compared with freshly isolated monocytes. Co‐culture with rlFN‐γ (40 h) reversed this decrease. Short‐term rlFN‐γ‐cultured cells, and fresh cells express similar numbers of FcγRII, and exhibit comparable FcγRII‐mediated ADCC activity. Phagocytic activity was not affected. Prolonged culture of monocytes for 9 days, co‐cultured with rlFN‐γ either from day 0 or from day 7, did not affect expression or functional activity of FcγRII. Furthermore, the effects were observed in both HR and LR individuals.Our results show that rlFN‐γ has strong effects on FcγRII‐mediated responses specifically during the early stages of monocyte maturation, most l

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02952.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

CD11b (Leu15) epitope is expressed on 20‐30% of peripheral blood lymphocytes, including CD16+large granular lytnphocytes and CD8+cells. This study confirms that 30% of CD8+lymphocytes and virtually all CD16+NK cells from healthy subjects express this determinant. In parallel, our data show that various proportions of CD3+4‐8‐, TCR‐δ cytotoxic T lymphoeytes and occasionally CD4+lymphocytes subsets could also express this epitope.The CD8+11b+phenotype is associated with suppression of T‐cell proliferative response and has been extensively used to characterize suppressor T lymphocytes. Since about 25% of CD8 lymphocytes are non‐T (CD3) and express the CD16 NK antigen (CD8+16+3 ‐), the expression of CD11b was also studied on CD8+3+T‐cell and CD8+16+NK‐cell subsets. To this end, we developed three methods using a flow cytometer equipped with a single laser and two fluorescence detectors. Results showed that T CD8+3+11b+and NK CD8+16+11b+lymphocytes account for 3O% and 70% of CD8+11b+cells respectively. Consequently, the CD8+3+11b+phenotype would be more specific for suppressor T lymphocytes than the total CD8+11b+phenotype which includes high proportion

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02953.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Antibodies against the α‐subunit of the acetylcholine receptor (AChR) are found in most patients with myaslhenia gravis and are considered to contribute to the receptor damage which leads to the characteristic signs and symptoms of the disease. This B‐cell response is T‐cell driven. Elevated T‐cell reactivities to AChR and its α‐subunit have been described in myasthenia gravis, and AChR α‐subunit peptide reactive T‐cell lines and clones preferentially recognizing certain defined sequence segments have been reported, thereby disclosing the possibility of specific immunotherapy. We have defined the T‐cell repertoire to AChR, its α‐subunit and the synthetic peptide sequences 1OO‐117,113‐130,143‐163,161‐179,207‐225,221‐240, and 235‐255 of the α‐subunit in an immunospot assay which is based on secretion of interferon‐gamma (IFN‐γ) by individual memory T cells upon stimulation with specific antigen in short‐term cultures. Most patients with myasthenia gravis displayed T‐cell reactivities to 1 to 6 different peptides. The mean numbers of T cells recognizing individual peptides varied in the myasthenia gravis patients between 1 per 77,000 and 1 per 167,000 peripheral blood mononuclear cells. None of the seven peptides evaluated could be identified as an immunodominant T‐cell epitope, and any of them was found to dominate in individual patients. The numbers of T cells reacting with AChR and recombinant human AChR α‐subunit were slightly higher (mean numbers 1 per 26,000 and 1 per 50,000 mononuclear cells, respectively). Such cells, as well as AChR α‐subunit peptide reactive T cells, were also found in patients with other neurological diseases and in healthy subjects, but at lower frequencies and numbers. In myasthenia gravis, the elevated numbers of memory T cells recognizing multiple AChR α‐subunit peptides may be crucial for the development of the disease, and the IFN‐γ rel

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02954.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effects of the administration of the recently discovered immunosuppressant 15‐Deoxysper gualin (DSP) on the development of insulin‐dependent diabetes mellitus (IDDM) in diabetes prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes‐prone BB rats as compared with the PBS‐injectcd controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+and OX6+splenocytes. Interruption of the treatment resulted in a later onset of diabetes in a high percentage of animals within 41 days. These findings suggest that 15‐DSP may temporarily reverse the pathogenic mechanisms leading to beta cell destruction and autoimmune diabetes in a well‐known experimental model of human insulin‐dependent diab

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02955.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Splenocytes from mice primed with influenza virus envelope proteins incorporated in iscoms, as micelles or as infectious virus, were restimulaled in vitro with the same antigen. Interleukin‐2 (IL‐2) and interferon‐gamma (IKN‐γ) were assayed in the supernatants of such cultures. Influenza virus iscoms induced IL‐2 and IFN‐γ responses in restimulation experiments that were antigen specific and significantly higher than those induced by micelles or infectious virus. Serum samples collected at the end of the experiments were analysed for the antibody response and profile. The antibody titres induced by iscoms were of a similar order of magnitude as those induced by infectious virus, and were about 18 times higher than the titres induced by micelles. In mice immunized with iscoms or infectious virus the most abundant antibodies were of the IgG1and IgG2a, isotype, and the IgE response was low. We conclude that immunization with iscoms stimulates the Th1‐like subtype of murin

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02956.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

It has previously been shown that synovial fluid (SF) mononuclear cells (MNC) from patients with reactive arthritis (ReA) and some patients with undifferentiated oligoarthritis (UOA) respond specifically to the triggering bacterium (specific responders). However, in some patients there is a response to two or more bacteria (non‐specific responders) and in a third group no response is found (non‐responders). We assessed whether the proportion of synovial MNC which were macrophage‐monocyte (MaMo) differed among the specific responder, non‐specific responder and non‐responder groups. There was no difference between the specific (33±9) and the non‐specific(32±26)groups; non‐responders had a higher percentage of MaMo (61.3±31%) although the difference was not significant. We also investigated whether the specificity of the response to antigen in ReA or UOA SF was altered by changing the T‐cell/MaMo ratio. In all five specific responders the immune response remained specific whatever the ratio tested. However, four of the five non‐specific responders, but none of the non‐responders, developed a specific response to one of the tested antigens by increasing the T cell/MaMo ratio. We conclude that in some patients with a non‐specific response, alteration of the T cell/MaMo ratio uncovers a specific response which may identif

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02957.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In myasthenia gravis the production of anti‐acetylcholine receptor antibodies is modulated by acetylcholine receptor‐specific T cells. Most B‐and T‐cell epitopes are located on the α‐subunit of the receptor. In order to map the fine specificity of the antigen‐specific T cells in myasthenia gravis, T‐cell stimulation in response to 70 hexapeptides was studied in 24 patients and 24 healthy individuals. The hexapeptides overlapped with one amino acid and represented residues 10‐84 of the NH2‐terminal part of the α‐subunit of the receptor. The IFN‐γ secretion from single T cells was used to detect T‐cell stimulation.A significanl difference in the T‐cell response to several of the peptides was found between patients and healthy controls. The majority of the hexapeptides induced T‐cell stimulation in at least one of the patients. Peptidc‐induced T‐cell stimulation was evident in all but one of the patients. The results indicate that different epitopes and multiple T‐cell clones are involved in the T‐cell rec

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02958.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

This study examined the production of an immunosuppressive factor by the KB and H191 human oral squamous carcinoma cell lines. Conditioned media (CM) from both cell lines markedly inhibited mitogen‐ and alloantigen‐induced proliferation of normal human and rat peripheral blood lymphocytes. By contrast, the proliferation of an exponentially‐growing fibroblast cell line remained unchanged by CM. The immunosuppressive factor appeared to act after lymphocyte commitment as indicated by continued blast cell formalion, the failure of CM to suppress resting lymphocytes and the fact that CM caused maximum inhibition of lymphocyte proliferation 72 h after the addition of PHA. The addition of exogenous IL‐2 did not counteract lymphocyte suppression. Inclusion of indomethacin and isoniazid during cell culture did not significantly alter the degree of suppressive activity. Mycoplasma contamination was absent and CM did not act directly with the thymidine or mitogen. The factor was heat stable at 50 C, acid labile and had a molecular weight in execss of 300 kDa. The results demonstrate that human oral squamous carcinoma cell lines produce an immunosuppressive factor that may have a role in tumour evasion of the host immune r

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02959.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY