Thymosin alpha 1 levels and helper:suppressor ratios in homosexual men.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
D L Mann
Publications and source records attributed to D L Mann.
Seminal fluid excretion of cytomegalovirus related to immunosuppression in homosexual men.
Seminal fluid samples from 84 Danish homosexual men were successfully cultured to determine the prevalence of cytomegalovirus excretion. Ten (15%) out of 66 men positive for the antibody were found to be excreting the virus. Although the proportion excreting was inversely related to age (p less than 0.01), three men aged over 30 and with many years of homosexual experience excreted the virus. In addition, a 50 year old man with Kaposi's sarcoma excreted the virus. A further study of the ratio of T cell helpers to suppressors in the men aged over 30 and a series of age matched non-excreting homosexual control or heterosexual men showed that those excreting cytomegalovirus in their seminal fluid had statistically lower ratios (all less than 0.77) than the controls (p less than 0.05). Excretion of cytomegalovirus may be related to re-emergence of latent infection in immunosuppressed homosexual men.
Adolescent↗
HLA and B-lymphocyte alloantigens in Gila River Indians.
HLA-A, B, C, DR, and MB and MT B-lymphocyte alloantigens were tested in 249 Pima and Papago Indians from Arizona. Frequencies of A and B locus antigens in Pimas were similar to published values for other North American Indians, as well as previous reports from Pimas. Cw3 was the most frequent C locus antigen found and DR5 was the most frequent DR antigen. Another B-cell specificity, DuB31, behaved as a DR allele and had a phenotype frequency of .717. This study is the first report of MB and MT frequencies in a North American Indian population, and the pattern of association with some DR antigens appears to be different from that observed in Europeans. MT3 had a phenotype frequency of .583, but was not associated with DR4, 7, 9, which suggests an undefined DR allele associated with MT3.
Adolescent↗
HLA DR alloantigens in different subsets of patients with Sjögren's syndrome and in family members.
Patients with Sjögren's syndrome alone (Ss), Sjögren's syndrome with rheumatoid arthritis (Ss-RA), and Sjögren's syndrome with Raynaud's phenomenon (Ss-RP) were typed for the HLA DR and MT antigens. Ss-RA patients had higher frequencies of HLA DR4 than did Ss patients. HLA-DR4 was also increased in frequency in patients with Ss-RP. This group of patients also showed increases in frequencies of HLA DR3. MT2 frequencies were elevated in all 3 patient groups, while MT1 was only increased in Ss. Three families with multiple individuals with Sjogren's syndrome were typed for HLA antigens. The affected individuals inherited unique combinations of haplotypes, suggesting the possibility of haplotype interaction in predisposition to disease.
Adult↗
In vitro lymphocyte proliferation response to therapeutic insulin components. Evidence for genetic control by the human major histocompatibility complex.
Genes in the major histocompatibility complex of mice and guinea pigs control immunologic responsiveness to insulins from other animal species. In order to determine if similar genetic control exists in man, we have examined lymphocyte proliferation responses to components of therapeutic insulins by employing lymphocytes from diabetic patients that receive insulin. Distinct groups of individuals demonstrated positive lymphocyte proliferative responses to beef insulin, beef and pork insulin, beef proinsulin, pork proinsulin, and protamine. Lymphocytes from the patient population were typed for the HLA-A, B, C, and DR antigens. An increased frequency of certain HLA antigens was found in those individuals that responded to the following therapeutic insulin components: beef, HLA-DR4; beef and pork, HLA-DR3; beef proinsulin, HLA-BW4, CW2, CW5, DR2, and DR5; protamine, HLA-CW3, CW5, and DR7. The results demonstrate that the human immune system recognized the structural differences between human and beef and/or pork insulin. These differences are two amino acids in the A chain, alpha loop, of beef insulin and the single terminal amino acid, alanine, which is common to pork and beef insulins. Positive responses to both beef proinsulin and pork proinsulin demonstrated the capability of restricted recognition of more complex proteins represented by the C-peptide in these insulin preparations. Lymphocyte proliferative responses to protamine were also restricted, which suggests a genetic control to this antigen. The association of these responses with HLA alloantigens strongly suggests that genes within the human major histocompatibility complex control recognition and lymphocyte response to therapeutic insulin components.
Adult↗
Cell surface antigen expression in newborn cord blood lymphocytes infected with HTLV.
Human T cell lymphocyte lines, established from lymphoid tissues from patients with adult T cell malignancies infected with the human T cell lymphoma virus (HTLV), were used in co-culture experiments to infect newborn cord blood lymphocytes (CBL). The infected and non-infected CBL cell lines were typed for HLA alloantigen determinants and tested for cell surface antigens using selected monoclonal antibodies. Infected cord blood lymphocytes showed inappropriate expression of alloantigenic determinants of the HLA-A and -B alleles. The monoclonal antibody 4D12, detecting an antigen common to the HLA-B5 cross-reactive group, was reactive with all infected cultures; this determinant appeared de novo in CBL cells lacking B5 cross-reactive group antigens in the uninfected state, and it increased in density in the infected cultures where the HLA-B5 cross-reactive alloantigens were present in uninfected CBL. HLA-DR was expressed in low levels or not detected on non-infected cultured cord blood lymphocytes and was present on all infected cells. OKT4 positive cells predominated in infected cultures, whereas OKT8 positive cells decreased in number or were absent. The TCGF receptor also increased both in density and in percent positive cells in all infected cell lines. The results suggest that HTLV may be tropic for a subset of T cells expressing mature T cell markers and that viral infections directly affect expression of cell surface antigens controlled by the human major histocompatibility complex (MHC).
Adult↗
Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies.
Antibodies which react with products encoded by the human DR locus precipitate a biomolecular membrane glycoprotein complex with m.w. of 29,000 and 34,000 daltons. Such antibodies are directed against HLA-DR Ia-like antigens found on human B cells and human monocytes and have been shown previously to inhibit a variety of in vitro cellular and humoral immune reactions. We have compared the in vitro effects of such antibodies on two assays of human immunity: antigen-specific proliferation and polyclonal immunoglobulin production. Intact IgG fractions of a rabbit heteroantiserum (anti-P29,34), a human MT-2 locus alloantiserum (Ia 172), and a mouse monoclonal antibody (LB 3.1) markedly inhibited in vitro immune reactivities of human mononuclear cells. Interestingly, F(ab')2 preparations of these antibodies failed to inhibit these in vitro immune responses at the concentrations tested. These data suggest that under certain conditions, Fc domains play a critical role in the inhibitory activity of antibodies to Ia-like molecules.
Animals↗
Familial chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his 5 offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in the other patients; the unaffected sibling developed lung adenocarcinoma. Cell surface analysis showed that 2 of these patients shared a common surface immunoglobulin profile with mu- and delta-type heavy chains and kappa-type light chains, whereas a 3d sibling with CLL had elevated mu- and kappa-chains. The patient with spontaneous disease remission had a perturbation in the percentage of cells bearing these same markers, consistent with a subclinical persistence of her lympho-proliferative process. Immunogenetic markers were associated with the occurrence of CLL, but these B-cell alloantigens were not linked to HLA. Two patients had abnormalities of chromosome 12 in B- but not T-cells: One had trisomy 12; the other had a mixture of dicentrics and translocations involving the same chromosome.
Aged↗
Heterogeneity of acute lymphocytic leukemia cell surface markers as detected by monoclonal antibodies.
Monoclonal antibodies 3A1, 4F2, 5E9, OKT3, OKT6, and OKT8 were tested by flow microfluorometry for reactivity with cells from patients with T-cell or null cell acute lymphocytic leukemia (ALL). The 3A1 antibody reacted with a greater percentage of cells from 1 group of patients that could be classified as T-cell leukemia patients as compared to its reaction in the group classifiable as null cell leukemia patients. Reactivity patterns of other monoclonal antibodies with lymphocytes from patients with ALL did not clearly define groups of ALL patients. All cells from individual leukemia patients reacted differently with the seven monoclonal reagents. On the basis of patterns of reactivity, T-cell leukemias could not be classified as malignant clones of cells from the previously described stages of thymus cell maturation. The results demonstrated that the cells undergoing malignant change express a variety of combinations of antigens not found on normal lymphocytes.
Antibodies, Monoclonal↗
Demonstration of a third structurally distinct human Ia beta chain by two-dimensional gel electrophoresis.
Previous studies have indicated that HLA-DR homozygous cell lines express two Ia alpha and Ia beta chains that combine to form at least two Ia molecules. This report demonstrates by two-dimensional gel electrophoresis the existence of a third structurally distinct human Ia beta chain on DR2 and DR5 cell lines. This suggests that at least five separate genes control the expression of Ia molecules on HLA-DR homozygous cell lines.
B-Lymphocytes↗
Association between Takayasu's arteritis and a B-cell alloantigen in North Americans.
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Adult↗
Amyl nitrite may alter T lymphocytes in homosexual men.
To evaluate the recent outbreak of Kaposi's sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells. In all eight AN users the fluorescence profile obtained with monoclonal antibody 9.6 (which detects the sheep E-rosette receptor) was bimodal, indicating a subpopulation of T cells with increased receptor density. A similar pattern was observed when OKT8, the antibody which detects cytotoxic suppressor cells, was used. Two of the seven men who did not use AN had abnormal fluorescence with reagent 9.6, and one of these also had a low H/S ratio. CMV-antibody titres were persistently high in fourteen of the fifteen healthy men, but the titres were not related to AN use of T-cell abnormalities. The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of DS and opportunistic infections in homosexual men.
Adult↗
High risk of sacroiliitis in HLA--B27-positive Pima Indian men.
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Age Factors↗
Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease.
The importance of late-onset congenital adrenal hyperplasia as a cause of hirsutism is controversial. Two of 35 women with a chief complaint of hirsutism met the criteria of 21-hydroxylase deficiency. In one, who presented with hirsutism, oligomenorrhea, obesity, infertility, and enlarged cystic ovaries, the initial diagnosis was polycystic ovarian syndrome. Family data showed that her disorder was autosomal recessive and linked to the histocompatibility leukocyte antigens (HLA), as in the classic form of congenital adrenal hyperplasia. Carriers were thus detectable by HLA typing. Thus late-onset congenital adrenal hyperplasia appears to be an allelic variant of congenital virilizing adrenal hyperplasia with a milder enzymatic defect. The diagnosis cannot be made clinically because the disease has the same presentation as idiopathic hirsutism or polycystic ovarian disease. Basal plasma 17-hydroxyprogesterone levels, unlike in classic congenital adrenal hyperplasia, can be normal, and an ACTH stimulation test or sequential measurements of plasma 17-hydroxyprogesterone throughout the day may be needed to show the abnormality. The incidence among hirsute women is estimated to be 6% to 12%, and the calculated gene frequency for the allele coding for attenuated expression of 21-hydroxylase deficiency is 0.015 to 0.057.
Adrenal Hyperplasia, Congenital↗
Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5.
The human class II, HLA-linked, B cell alloantigens include the HLA-DR, MB, MT, and Te determinants. Interest in the molecular relationships of these antigens has recently intensified because of their homology to the murine Ia antigens and their possible importance in disease predisposition and transplantation. We have used alloantisera with carefully defined immunochemical as well as serologic specificity, and two immunochemical techniques, sequential immunoprecipitation with analysis by SDS-PAGE and two-dimensional gel electrophoresis, to explore the molecular relationships of the MT2, MB3, MT4, and HLA-DR5 antigenic determinants. The data presented here indicate that 1) all class II molecules that bear the DR5 antigenic determinant also bear the MT2 antigenic determinant; (2) the homozygous DR5 cell line, Swei, expresses at least two structurally distinct class II molecules, both of which bear MT2: one bears the MT2, MB3, and MT4 antigenic determinants, and the second bears the MT2, but not the MB3 or MT4 antigenic determinant; and (3) the DR5 determinant is located on at least one and possibly both of these distinct class II molecules.
Absorption↗
Evidence that antisera that react with products of the human HLA-DR locus may block in vitro antigen-induced proliferation by inducing suppression.
It is widely recognized that antisera that interact with determinants encoded by the Ia region of the mouse and its counterpart, the DR locus of man, are capable of interfering with the ability of monocytes and lymphocytes to respond in vitro to an antigenic stimulus. Using an in vitro assay that measures antigen-specific proliferation of human lymphocytes, we found that both a heteroantiserum raised in rabbits (anti-P29,34) and alloantisera which recognize determinants encoded for by the human DR locus dramatically block in vitro antigen-specific proliferation. These anti-DR antisera appear to act at the level of the monocyte; monocytes pulsed and washed free of excess antisera fail to promote proliferation in the presence of soluble antigen and untreated T cells whereas identically pulsed and washed T cells respond normally with untreated monocytes. Furthermore, the addition of unpulsed monocytes fails to restore in vitro antigen-specific reactivity. Our data suggest that membrane-bound anti-DR-specific antisera on monocytes is profoundly suppressive, and also suggests simple steric hindrance may not account for all of the observed effects such antisera have on monocyte-T cell interactions.
Antibody Affinity↗
Ankylosing spondylitis and systemic lupus erythematosus: a rare HLA combination.
The condition of a 43-year-old man fulfilled the strict diagnostic criteria for both ankylosing spondylitis and systemic lupus erythematosus. To our knowledge, this is the fist verified report of the concurrence of these rheumatic diseases. An unusual combination of genetically determined markers seems to have caused an increased risk for the development of both disorders.
Adult↗
HLA-A2 and type 2 (insulin independent) diabetes mellitus in Pima Indians: an association of allele frequency with age.
In Pima Indians with Type 2 (insulin independent) diabetes mellitus, HLA-A2 allele frequencies were inversely associated with age, (0.72, 0.59, and 0.52 in those less than 35, 35 to 54, and 55 years old and over, respectively). This suggests that there may be a gene closely linked with the HLA-A locus which plays a role in the expression of diabetes in the Pimas by contributing to an earlier age of onset. HLA-A2 was found in 65% non-diabetic and 81% of 191 diabetic subjects (relative risk = 2.2).
Adult↗