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Novel carbohydrate antigen expressions were observed on T lymphocytes from HIV infected patients using flowcytometric analysis with four mAbs; BM-1, ACFH-18, FH-2 and C-6. These carbohydrate antigens were also expressed on oncogenic transformed cells but were either not expressed or were weakly expressed in lymphocyte populations from healthy subjects. A dramatic change in glycosylation was induced on CD8+T cells from HIV infected patients. The glycosylation change correlated with the progression of the disease. The incidence of Ley antigen expression on CD8+T cells increased as the disease progressed with the ongoing impairment of immune function. The phenotype change that occurred with Ley antigen expression might reflect the abnormal activation of T lymphocytes of some specific, but unknown, population of CD8+T cells. Thus, carbohydrate changes on the cell surface may induce immunological abnormality and accelerate the damage within the CD4+T cell subset, resulting in an impairment of the antigen specific immune system.

We have been developing a new treatment for patients with rheumatoid arthritis (RA) by using intradermal injection of carbohydrate molecule complex. Among them, tumor cell associated glycoconjugate (TCA), the membrane structure of Kato III is one of the effective molecules. We studied the immunomodulatory effect of TCA on the autologous mixed lymphocyte reaction (AMLR) using PWM-mitogen induced lymphoblasts as stimulator cells and peripheral blood mononuclear cells (PBMC) as responder cells. In the kinetic study of the AMLR, its maximum proliferation was observed on days five through seven and responding CD4 cells highly expressed HLA-DR antigen. Studied AMLR in 10 patients with RA, proliferative responses of AMLR in these patients were divided into two types, high and low AMLR types. In vitro examination of TCA on AMLR showed that TCA at a concentration of 250 ng/ml significantly suppressed the AMLR response (p less than 0.01, paired T-test) and this phenomenon was found more frequently in high AMLR type patients than in low AMLR type patients. The suppressive effect of TCA on AMLR had a tendency to correlate with the efficacy of TCA therapy in patients studied. These results suggest that TCA may play a role in regulating the function of autoreactive lymphocytes of patients with RA.

In order to analyse the diversity of T-cell receptors (TCRs) expressed by the T-cell population activated by allogeneic HLA-DR stimulation, TCRβ cDNA was synthesized from mRNA of human CD4+ T cells that had been stimulated in a primary mixed lymphocyte reaction (MLR). The TCRβ cDNA was amplified by the polymerase chain reaction (PCR), subjected to bacterial cloning, and sequenced from Vβ through Jβ. Twenty-six different Vβ genes and 10 different Jβ segments were detected among 56 randomly selected cDNA clones. Occurrences of Vβ317.1 and Jβ1.5 were higher than those found in the CD4+ T-cell population activated with a CD3-specific antibody. A total of 53 different CDR3 sequences, two of them occurring more than once, were detected among the 56 cDNA clones. In order to estimate the degree of CDR3 diversity, amino acid similarity in the CDR3 region of the cDNA was calculated and compared with those of the anti-CD3-activated T-cell sequences as well as those of various published T-cell clone sequences, each directed to either alloantigens or single antigenic peptides. It was found that the similarity score among CDR3 sequences obtained from the MLR (56.4 ± 10.3) was comparable to those of anti-CD3-activated T cells (55.7 ± 10.7) and those of T-cell clones directed toward alloantigens (range, 48.4 ± 12.4-59.4 ± 13.1), but significantly smaller than those of T-cell clones directed toward single antigenic peptides such as those derived from myelin basic protein (75.6 ± 17.9) and cytochrome c (76.9 it 20.5). These results provide quantitative proof that TCRs of T cells activated by primary allogeneic HLA-DR stimulation have a larger diversity than those recognizing single antigenic peptides. [ABSTRACT FROM AUTHOR]

In the sera of ten normal humans and twenty-eight candidates for organ transplantation; the passive haemagglutination test detected a 50%, incidence of preformed antibodies of low litre directed against horse serum, Such antibodies were also found to cross react with goat or rabbit sera in most instances, Seventeen of the organ recipients were later studied after the institution of treatment with horse antihuman-lymphocyte globulin (ALG). The incidence of anti-horse-serum antibodies rose to 100%. At the same time, an increased activity against goat serum developed; cross-reactions against rabbit serum were also demonstrated but to a less pronounced degree. With immunoelectrophoresis and Ouchterlony diffusion tests, it was shown that the cross-reactivity was to similar although not necessariIy identical protein components of the different heterologous sera. These data suggest that there is an inherent risk in switching from one ALG to another, particularly if horse and goat derivatives are used sequentially. Since rabbit ALO does not cross react so extensively with horse or goat serum it would be predicted to be a relatively safer second-line agent. These expectations seemed to have been realized in six patients who were given more than one kind of ALG always beginning with horse globulin. When goat ALG was administered second, anaphylactic reactions tended to appear early, but when the rabbit product was given second or third, it was relatively well tolerated. [ABSTRACT FROM AUTHOR]