Biomedical subjects

D L Rudolph

Publications and source records attributed to D L Rudolph.

At least 37 records · Page 2Linked to original sources

PubMed1994

Modulation of HTLV-II-associated spontaneous lymphocyte proliferation by beta 2 integrin CD11a/CD18 involves interaction with its cognate ligand, CD54.

In vitro culture of lymphocytes from persons infected by human T-lymphocyte virus type II (HTLV-II) results in spontaneous proliferation in the absence of any exogenous stimuli. The present investigation examined the role of integrin molecules in spontaneous lymphocyte proliferation (SLP) in persons infected with HTLV-II (n = 18) and normal controls (n = 16). Phenotypic analysis of SLP cells on Day 8 demonstrated no change in the surface expression of CD29 (beta 1), CD49b,d,e, and f (alpha-chains) compared with cells from normal controls; however, there was an increase of CD29 expression on SLP cells on Day 8 (77.2 +/- 5.1%) compared with Day 0 (53.2 +/- 3.1%; P < 0.01). Furthermore, addition of extracellular matrix proteins, fibronectin, laminin, or collagen (beta 1 integrin ligands) did not alter either the proliferative responses or the adhesion clusters in either groups. Analysis of beta 2 integrins on SLP cells showed not only an increased cell surface density of both CD18 and CD11a but also differential expansion of CD8+ T-cells coexpressing CD18 (54.0 +/- 10.3%), CD11a (53.7 +/- 8.1%), and S6F1, an epitope of CD11a, (65.3 +/- 7.8%) on Day 8 compared with Day 0 (20.0 +/- 2.5%, 19.3 +/- 1.9%, and 38.0 +/- 7.0%, respectively). Monoclonal antibodies to CD18 and CD11a inhibited SLP by 55 +/- 6.3% in HTLV-II-infected persons in a dose-dependent manner. The inhibition of SLP by anti-beta 2 antibodies was not due to negative signaling, since these antibodies did not inhibit anti-CD3-stimulated proliferation of normal lymphocytes. Moreover, monoclonal antibodies to CD54, the ligand for CD11a, inhibited the SLP in the majority of HTLV-II-infected persons studied. Taken together, these data suggest that SLP by PBL from HTLV-II-infected individuals is mediated through increased expression of beta 2 integrins that can modulate cognate receptor/ligand interactions on the cell surface of autologous proliferating cells.

Antigens, CD↗

PubMed1994

Enhancing exercise adherence in middle-aged males and females.

BACKGROUND: Perceptions of personal efficacy have been consistently identified as being determinants of exercise adherence in asymptomatic, rehabilitative, younger, and older populations. The present study incorporated a randomized control design in an effort to examine the effects of an efficacy-based intervention in enhancing exercise adherence in a large sample (N = 114) of formerly sedentary middle-aged males and females. METHODS: Subjects randomly assigned to an exercise plus intervention group or an exercise plus attentional control group participated in a 5-month long walking program led by trained personnel. Exercise behavior (frequency, miles walked, duration) were assessed on a continuous basis and self-efficacy was measured at 1, 2, and 4 months. RESULTS: Repeated measures multivariate analyses revealed a significant treatment effect with subjects in the intervention group exercising more frequently, for longer duration, and walking greater distances over the course of the program. Path analysis indicated that the effect of the treatment on adherence was direct rather than through self-efficacy as hypothesized. Self-efficacy was, however, a significant predictor of exercise behavior in the early and middle stages of the exercise program but not during the last month. CONCLUSIONS: An intervention program designed to maximize information pertaining to participants' capabilities appears to have had a reasonable effect on reducing attrition in middle-aged males and females and self-efficacy was a significant predictor of exercise frequency over time. Further research efforts are required to tease out those cognitive factors that might underlie any effects of interventions in exercise adherence.

Attitude to Health↗

PubMed1994

Viral-specific humoral immune responses following transfusion-related transmission of human T cell lymphotropic virus type-I infection.

The immunoglobulin (Ig) isotypes of antibodies to specific proteins of the human T cell lymphotropic virus type I (HTLV-I) were determined by Western blot analysis of serial specimens from six individuals who experienced HTLV-I seroconversion following blood transfusion; five remained asymptomatic carriers, while one developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 32 weeks posttransfusion. Analysis of Ig isotypes demonstrated that while IgM was the most frequent early response to gag (p19, p24) and env (r21e) proteins within the first 3 months following transfusion, IgG and IgA responses could also be detected within this period. HTLV-I-specific antibody responses plateaued in all Ig isotypes, including IgM, within the next 4- to 6-month period following transfusion and persisted through the entire study period (> 4 years). Comparison of antibody profiles in Ig isotypes and IgG1 and IgG3 subclass among asymptomatic carriers and one individual who developed HAM/TSP demonstrated no evidence of isotypic prominence or IgG subclass restriction in either group. These results indicate the appearance of HTLV-I-specific IgM that persists even after the primary infection and suggest that such response does not appear to provide an early marker of seroconversion. Further, we found no evidence of isotypic prominence or restriction of the antibody response in recipients who remained asymptomatic compared to one who developed HAM/TSP.

Blotting, Western↗

PubMed1994

Differential immune responsiveness to the immunodominant epitopes of regulatory proteins (tax and rex) in human T cell lymphotropic virus type I-associated myelopathy.

Infection by human T cell lymphotropic virus type I (HTLV-I) is etiologically linked with HTLV-I-associated myelopathy (HAM) or adult T cell leukemia (ATL). To evaluate the contribution of the viral regulatory proteins tax and rex during the development of disease, antibody responses to these proteins were analyzed in patients with HAM (n = 28) or ATL (n = 48) and in asymptomatic carriers (n = 69). Epitope mapping analysis identified immunodominant epitopes towards the amino terminus (Tax8(106-125)) and at the carboxyl terminus (Tax22(316-335), Tax23(331-350), and Tax24(336-353)) of tax and the amino terminus (Rex1(1-20), Rex2(16-35), Rex4(46-65), and Rex6(76-95)) of rex. Analysis of antibody reactivity to these immunodominant epitopes demonstrated preferential reactivity to Tax8, Tax22, Tax23, and Tax24 (71%-93%) and to Rex4 and Rex6 (52%) in patients with HAM when compared with reactivities in ATL patients (4%-31% for tax and 19%-24% for rex) or asymptomatic carriers (27%-37% for tax and 7%-23% for rex). In contrast, antibody responses to the immunodominant epitopes of the env proteins of HTLV-I (MTA, Env1, Env5) were similar in all of three clinical groups. Thus, differential immune responsiveness to the immunodominant epitopes of tax and rex in patients with HAM may play a role in disease pathogenesis in HTLV-I-infected persons.

Amino Acid Sequence↗

PubMed1994

Detection of antibodies to trans-activator protein (p40taxI) of human T-cell lymphotropic virus type I by a synthetic peptide-based assay.

Antibodies to human T-cell lymphotropic virus type I (HTLV-I) trans-activator protein (p40taxI) were determined in serum specimens from individuals infected with HTLV-I (n = 138) and HTLV-II (n = 19). Western blot (immunoblot) analysis using recombinant tax demonstrated the presence of anti-tax antibodies in 96% of patients (25 of 26) with HTLV-I-associated myelopathy, 43% of those (20 of 46) with adult T-cell leukemia, and 61% of asymptomatic HTLV-I blood donors (40 of 66); only one of the HTLV-II specimens reacted with the recombinant tax protein. Synthetic peptides (Tax8(106-125), Tax22(316-335), Tax-23(331-350), and Tax-24(336-353) representing the immunodominant epitopes of p40taxI detected anti-tax antibodies in 66 (48%), 50 (36%), 66 (48%), and 64 (46%) of 138 HTLV-I-positive specimens, respectively. An enzyme immunoassay using an equimolar ratio of these four peptides allowed sensitive detection of anti-tax antibodies in 96% of patients (25 of 26) with HTLV-1-associated myelopathy, 52% of adult T-cell leukemia patients (24 of 46), and 62% of asymptomatic HTLV-1-infected donors (41 of 66). The synthetic peptide-based cocktail assay was HTLV-I specific, since none of the HTLV-II-infected specimens reacted with these peptides. Interestingly, the corresponding regions from the HTLV-II tax protein, Tax8II(106-125), and Tax-22II(312-331) did not react with either HTLV-II or HTLV-I specimens. Thus, a synthetic peptide-based assay composed of immunodominant epitopes located towards the amino terminus and the C terminus of p40taxI provides a reliable and sensitive assay for the detection of anti-tax antibodies in seroepidemiologic studies.

Amino Acid Sequence↗

PubMed1993

Isolation, characterization, and transmission of human T-lymphotropic virus types I and II in culture.

Highly sensitive coculture methods were developed both for isolation of human T-lymphotropic virus types I and II (HTLV-1 and HTLV-II) from infected individuals and for productive infection of lymphoid cells. Mitogen-activated peripheral blood mononuclear cells (PBMC) from 13 HTLV-I- and 20 HTLV-II-positive specimens were cocultured with an equal number of mitogen-activated PBMC from HTLV-seronegative individuals, and culture supernatants were tested for the presence of soluble p24gag antigens at weekly intervals for 4 weeks. Eleven of 13 (85%) HTLV-I and 14 of 20 (70%) HTLV-II cultures were positive for p24 antigens. None of the 17 HTLV-seroindeterminate or six HTLV-seronegative specimens were positive for the presence of p24 antigen. The isolation rates for HTLV-I and HTLV-II by an alternative whole-blood lysis procedure were comparable to those obtained by standard PBMC cultures. Furthermore, cocultivation of PHA-stimulated PBMC from healthy donors with lethally irradiated HTLV-I- and HTLV-II-infected cell lines (SP and Mo-T, respectively) resulted in productive viral infection, as reflected by the appearance of p24gag antigens concomitant with specific genomic amplification of HTLV proviral DNA after 3 weeks of cocultivation. Thus, the cocultivation technique provides a highly sensitive and specific procedure both for HTLV isolation and for infection of target cells.

Base Sequence↗

PubMed1993

Over expression of insulin-like growth factor receptor type-I in T-cell lines infected with human T-lymphotropic virus types-I and -II.

To determine if aberrant expression of tyrosine kinase growth factor receptors may be related to the cell transformation capabilities of human T-lymphotropic viruses (HTLVs), we examined the expression of the epidermal growth factor receptor (EGF-R), insulin receptor (INS-R), and insulin-like growth factor receptor type-I (IGFR-I) in cell lines infected with HTLV type I (MT-2, HuT-102) and HTLV type II (Mo-T). Levels of mRNA transcripts for IGFR-I were significantly higher in both MT-2, HuT-102 (HTLV-I) and Mo-T (HTLV-II) cell lines than in uninfected cell lines (HuT-78, Jurkat); no detectable levels of EGF-R or INS-R mRNA transcript were observed in HTLV-infected or uninfected cell lines. Southern blot analysis demonstrated that no amplification or rearrangement of the IGFR-I gene occurred in either the MT-2 or Mo-T cell line. Flow cytometry analysis demonstrated that while IGFR-I protein was constitutively expressed on the cell surface in both MT-2 and Mo-T cell lines, neither EGF-R nor INS-R proteins could be detected. Ligand binding studies with MT-2 and Mo-T cell lines demonstrating binding of 125I insulin-like growth factor type-1 (IGF-I) in a dose-dependent manner and this response could be inhibited by increasing concentrations of cold IGF-I. These data demonstrate that deregulated expression of functional IGFR-I, the regular component of the growth control machinery of normal cells, may contribute to cellular proliferation and eventual transformation in HTLV-I- and HTLV-II-infected cell lines.

Cell Transformation, Viral↗

PubMed1993

Characterization of human T-lymphotropic virus type I- and II-infected T-cell lines: antigenic, phenotypic, and genotypic analysis.

Eighteen long-term T-cell lines were established from peripheral blood mononuclear cells of individuals infected with human T-lymphotropic virus type I (HTLV-I) or II (HTLV-II). These cell lines (10 HTLV-I and 8 HTLV-II), representing diverse pathologic profiles and geographic regions, have been in culture for over 6 months and have constitutively produced p24gag antigen. Antigenic characterization of the cell lines by Western blot analysis demonstrated that all but one produced gag (p24) and env (gp46 or gp52) structural proteins; one HTLV-I-infected cell line exhibited an aberrant protein profile. Phenotypic analysis of the HTLV-infected cell lines demonstrated phenotypes consistent with activated T-cells (CD5+, CD25+, HLA-DR+). The HTLV-I-infected cell lines were predominantly CD4+ (IR, FS, A212, SP, 1657, 1742, 3669, 1996, and 3614), whereas EG was CD8+. The HTLV-II-infected cell lines were either CD4+ (H2A, Y17, G12.1), CD8+ (H1H, H2E, Y03, Y06), or both (H1B). Restriction map analysis and subtyping of the viral genomes demonstrated heterogeneity among these isolates. Of the HTLV-I-infected cell lines, six were subtype II, one was subtype III and, on the basis of additional restriction sites, another subtype, tentatively classified as subtype IV, could be identified for three of the HTLV-I-infected cell lines. Of the HTLV-II-infected cell lines, six were subtype HTLV-IIa and two were subtype HTLV-IIb. While the majority of the cell lines resemble the prototypic HTLV-I-infected (MT-2) and HTLV-II-infected (MoT) cell lines, the antigenic, phenotypic, and genotypic data collectively demonstrate heterogeneity among viral isolates representing diverse geographic regions.

Adult↗

PubMed1993

Detection of human T-lymphotropic virus type-I/II env antibodies by immunoassays using recombinant fusion proteins.

Two recombinant fusion proteins representing the C-terminus of the envelope glycoprotein of HTLV-I (rEnv-93(201-440)) and the C-terminus of the external glycoprotein (RE-3(165-306)) were tested in a Western blot (WB) assay for their ability to detect the presence of env antibodies in serum specimens from HTLV-I (n = 27) and HTLV-II (n = 22) infected individuals. The rEnv-93 reacted with 27 (100%) of 27 HTLV-I-infected specimens and 19 (86%) of 22 of HTLV-II-infected specimens. In contrast, RE-3 reacted with 25 (93%) of 27 HTLV-I-infected specimens, and only six (27%) of 22 HTLV-II-infected specimens, thus demonstrating predominant reactivity with HTLV-I compared with HTLV-II. Because of the high sensitivity of rEnv-93 reactivity in both HTLV-I and HTLV-II, the specificity of this env protein was evaluated in specimens with isolated gag reactivity (HTLVind). Of the 44 HTLVind specimens, four (9%) demonstrated reactivity to rEnv-93 in WB assay. We, therefore, conclude that although rEnv-93 is highly sensitive for detection of env protein, it has the potential to yield some false-positive reactions presumably due to the conserved nature of retroviral transmembrane epitopes.

Amino Acid Sequence↗

PubMed1993

Human T lymphotropic virus type II (HTLV-II) infection among female prostitutes in Yucatan, Mexico.

The antibodies to human T-lymphotropic virus type I/II (HTLV-I/II) were determined in non-intravenous drug-using female prostitutes from Merida Yucatan, Mexico. Serum specimens from 282 female prostitutes collected during 1990 were tested initially by enzyme immunoassay and further confirmed by western blot assays. Of these, 5 (1.8%, 95% confidence interval 0.2 to 3.3) were shown to be HTLV-I/II positive (reactivity to p24gag and gp68/r21eenv). All five specimens were shown to be infected with HTLV-II by immunoassays using type-specific synthetic peptides and recombinant proteins. Long-term cell lines developed from two individuals demonstrated active viral replication and were of CD8 phenotype. Polymerase chain reaction analysis from four of these five prostitutes demonstrated HTLV-II-specific amplification of all four specimens, of which one was subtype a (HTLV-IIa) and three were subtype b (HTLV-IIb). These data show that HTLV-II is the predominant HTLV type among female prostitutes from the Yucatan.

Adolescent↗

PubMed1993

Discrimination of human T-lymphotropic virus type-I and type-II infections by synthetic peptides representing structural epitopes from the envelope glycoproteins.

Synthetic peptides representing the immunodominant structural motifs of the envelope region of human T-lymphotropic virus types I (HTLV-I) (Env-1(191-214) and Env-5(242-257)) and II (HTLV-II) (Env-20(85-102 and Env-2(187-209)) were used to develop an enzyme immunoassay that could discriminate between HTLV-I and HTLV-II. Serum specimens from individuals whose infections were confirmed and typed by means of the polymerase chain reaction (PCR) were used to determine the sensitivity and specificity of the new assay. When 73 PCR-confirmed HTLV-I specimens were tested with the HTLV-I peptides, the absorbance values for 71 (97.3%) were at least two times higher than the values obtained with the HTLV-II peptides; these samples thus were classified as HTLV-I. Two specimens reacted with all the peptides and, therefore, could not be typed. Conversely, when 59 PCR-confirmed HTLV-II specimens were tested with the HTLV-II peptides, 55 (93%) produced high absorbance values and were typed as HTLV-II; 4 specimens could not be typed. None of the specimens was incorrectly typed; hence, the specificity of this assay was 100%. When this assay was compared with other HTLV immunoassays, the degrees of sensitivity and specificity were similar. The main advantage of this new assay is that synthetic peptides representing variant sequences can easily be added as new variant HTLV strains are identified.

Amino Acid Sequence↗

PubMed1992

Characterization of a B-cell immunodominant epitope of human T-lymphotropic virus type 1 (HTLV-I) envelope gp46.

The immune response elicited by a synthetic peptide derived from an immunodominant external envelope region (Env-5, amino acids 242-257) of human T-lymphotropic virus type 1 (HTLV-I) was tested in a rabbit model of HTLV-I infection. The synthetic peptide elicited a strong antibody response to the HTLV-I envelope protein gp46; however, these antibodies failed to inhibit HTLV-I-mediated cell fusion. Immunized rabbits were not protected from HTLV-I infection as determined by seroconversion to viral core proteins by immunoblot, HTLV-I p24 antigen detection in lymphocyte cultures and polymerase chain reaction for the HTLV-I provirus in lymphocyte DNA. Env-5 peptide immunization failed to induce T-cell lymphocyte proliferative responses in rabbits, but induced antibody responses in T-cell deficient Balb c nu/nu mice suggesting that the antigenic determinant represented by the Env-5 peptide is primarily a B-cell epitope. These results further define an immunodominant epitope of the HTLV-I envelope protein and suggest that potential synthetic peptide vaccines against HTLV-I infection must contain multiple antigens that induce both humoral and cellular immune reactivity.

Animals↗

PubMed1992

Failure to detect evidence of human T-lymphotropic virus (HTLV) type I and type II in blood donors with isolated gag antibodies to HTLV-I/II.

Of the 267,650 blood donations from members of the US armed forces, 72 (0.027%) were serologically confirmed to be positive for human T-lymphotropic virus type I/II (HTLVpos) and 379 (0.14%) were Western blot (WB)-indeterminate with banding pattern restricted to the proteins encoded by the gag gene only (HTLVind). To determine whether these apparently healthy HTLVind blood donors are infected with HTLV-I or HTLV-II, coded specimens from randomly selected military blood donors (n = 73) were tested for antibodies to HTLV by WB and radioimmunoprecipitation assay (RIPA) using HTLV-I (MT-2) antigens, by enzyme immunoassay using synthetic peptides representing the immunodominant epitopes of HTLV, and for sequences of proviral HTLV DNA by the polymerase chain reaction (PCR). Of the 73 HTLVind donors, none showed presence of env reactivity by HTLV WB and RIPA. Minimal reactivity was observed with synthetic immunodominant motifs derived from the env protein of HTLV-I (Env-1(191-214) and Env-5(242-257)) or HTLV-II (Env-2(187-209) and Env-20(85-102)) and gag protein (Gag-1a(102-117) and Gag-10(364-385)). A peptide corresponding to the endogenous retroviral sequence with structural homologies to the gag protein of HTLVs (RTVLgag) reacted with antibodies not only in HTLVpos (88%) and HTLVind (42% to 66%) specimens, but also reacted with normal control subjects (60%). Furthermore, none of the 73 HTLVind specimens demonstrated presence of the HTLV genome when amplified with primers for the pol and tax/rex region. Six to 23 months from the initial test, 27 subjects still gave indeterminate WB patterns, and 13 of these repeat specimens were still negative for the presence of HTLV genome. We conclude that individuals at low risk for HTLV infection who have HTLVind WB reactivity are rarely, if ever, infected with HTLV-I or HTLV-II.

Amino Acid Sequence↗

PubMed1992

Phenotypic expression of integrin membrane receptors on spontaneously proliferating CD8 cells in human T-lymphotropic virus type II (HTLV-II)-infected individuals.

Spontaneous lymphocyte proliferation in the absence of exogenous stimulators was examined in asymptomatic HTLV-II-seropositive (n = 12) and seronegative individuals (n = 16). Mean spontaneous lymphocytic proliferation significantly increased on day 8 postculture in HTLV-II-infected individuals (5762 +/- 899 cpm) compared with normal controls (2034 +/- 925 cpm, P less than 0.01). The proliferating cells in infected individuals were predominantly T cells; neither B cells nor monocytes demonstrated any proliferation. Phenotypic analysis of cultured cells from individuals with HTLV-II infection demonstrated differential expression of integrin molecules as defined by anti-CD29 and anti-S6F1 (42.8 +/- 4.2 and 39.6 +/- 5.9%, respectively) on CD8 cells, as compared with day 0 peripheral blood mononuclear cells (PBMC) from infected individuals (19.7 +/- 3.5 and 19.9 +/- 1.9%, respectively) or normal controls (12.9 +/- 3.1 and 11.5 +/- 2.5%, respectively; P less than 0.001 for both comparisons). These CD8+ cells did not express CD16 or CD11b. The culture supernatants derived from the spontaneously proliferating cells had significantly increased levels of sCD8 and sCD25 (765 +/- 180 and 1805 +/- 320 U/ml, respectively) compared with those from normal controls (222 +/- 120 and 305 +/- 90 U/ml, respectively; P less than 0.01). Furthermore, culture supernatants derived from spontaneously proliferating PBMC from HTLV-II-infected individuals had no detectable levels of HTLV antigen and did not stimulate proliferation of PBMC from normal donors. These results suggest that the spontaneous proliferation in HTLV-II asymptomatic carriers is due to expansion of CD8 cells expressing integrin receptors which may serve as costimulatory molecules for their activation.

Adult↗

PubMed1992

Identification of immunodominant epitopes in envelope glycoprotein of human T lymphotropic virus type II.

A series of synthetic peptides derived from the envelope glycoprotein of human T lymphotropic virus type II (HTLV-II) was used in an enzyme immunoassay to determine the immunodominant epitopes of envelope glycoprotein. Of the 11 synthetic peptides spanning the external glycoprotein of HTLV-II (gp52) and the 3 from the transmembrane protein (gp21), 3 peptides from gp52 (termed Env-20(85-102), Env-202(173-209), and Env-203(219-256] reacted with most of the polymerase chain reaction-confirmed HTLV-II specimens (83, 95, and 76%, respectively); all other peptides reacted minimally with these specimens. Env-202(173-209) reacted with a greater percentage (91 to 100%) of specimens from different risk groups, including intravenous drug users (n = 30), North American Indians (n = 13), Guaymi Indians from Panama (n = 22), and routine U.S. blood donors (n = 34), when compared with Env-20(85-102) (73 to 100%) or Env-203(219-256) (68 to 83%). Furthermore, Env-20(85-102) and Env-202(173-209) had some reactivity (8-25%) with sera from HTLV-I-infected individuals, whereas Env-203(219-256) reacted with 58% of HTLV-I specimens. We conclude that peptides Env-20(85-102) and Env-202(173-209) represent the type-specific immunodominant epitopes of HTLV-II external glycoprotein.

Amino Acid Sequence↗

PubMed1992

Humoral responses to the immunodominant gag and env epitopes of human T-lymphotropic virus type I among Melanesians.

The immune responsiveness to the immunodominant B-cell epitopes of human T-lymphotropic virus type I (HTLV-I), derived from the external envelope glycoprotein (recombinant MTA-1(162-209), synthetic Env-1(194-214), and Env-5(242-257)) and the gag-encoded matrix protein (Gag-1a(102-117)), was analyzed in 19 HTLV-I-seropositive and 51 HTLV I-seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands. The reactivities of seropositive Melanesian specimens to MTA-1 (100%), Env-5 (89%), and Gag-1a (79%) were similar to that seen with U.S. specimens, while reactivity to Env-1 was lower in Melanesian specimens (68%). Minimal reactivity was found to the env epitopes among the 51 HTLV-I-seroindeterminate Melanesians, but 29 (57%) reacted to Gag-1a. The failure to detect HTLV-I gag, pol, env, and tax gene sequences by polymerase chain reaction among the seroindeterminate Melanesians suggests that such reactivities to the Gag-1a epitope represent cross-reacting antibodies with closely related microbial or cellular proteins.

Amino Acid Sequence↗

PubMed1992

Spontaneous proliferation of HTLV-II-infected peripheral blood lymphocytes: HLA-DR-driven, IL-2-dependent response.

Peripheral blood lymphocytes obtained from HTLV-II-infected persons (n = 13) and cultured in the absence of exogenous stimulator demonstrated augmented spontaneous proliferation (17,672 +/- 5,498 cpm) when compared with cells from healthy donors (1,921 +/- 1,306 cpm). Removal of non-T population did not abrogate the proliferative response of patients' PBMC, suggesting that the proliferation is not related to the autologous mixed lymphocyte reaction. Addition of recombinant interleukin-2 (rIL-2; 0.1 U/ml) to spontaneously proliferating cultures from HTLV-II-infected persons resulted in a 3- to 4-fold increase in proliferation (61,985 +/- 16,003); in contrast, PBMC from controls demonstrated 38- to 42-fold increase in their proliferative capacity in response to rIL-2 (77,256 +/- 13,044). Antibodies to both IL-2 receptor and HLA-DR were able to inhibit the spontaneous proliferation of PBMC from HTLV-II-infected persons in a dose-dependent manner. Furthermore, addition of cyclosporin A, which preferentially blocks accumulation of IL-2 mRNA, also inhibited spontaneous proliferation in a dose-dependent manner. These observations suggest that the spontaneous proliferation of HTLV-II-infected PBMC is at least in part an HLA-DR-driven, IL-2-dependent event, which is not analogous to the AMLR.

Adult↗

PubMed1992

Concomitant augmentation of CD4+ CD29+ helper inducer and diminution of CD4+ CD45RA+ suppressor inducer subset in patients infected with human T cell lymphotropic virus types I or II.

To examine the immunomodulatory effects of HTLV infection, lymphocyte subset analysis was performed on patients infected with human T cell lymphotropic virus type-I (HTLV-I, n = 6) or -II (HTLV-II, n = 12) and on normal blood donors (n = 16). The percentages of total B lymphocytes (CD19), natural killer (NK) cells (CD16), T lymphocytes and their subsets (CD2, CD3, CD4, CD5, CD7, CD8), and IL-2R (CD25) were found to be within the range found in normal donors. However, the expression of CD8+ HLA-DR+ increased significantly in patients with HTLV-I or HTLV-II infection (14.1 +/- 3.9% and 9.7 +/- 2.4% respectively; P less than 0.01) when compared with controls (3.2 +/- 1.1%). In addition, there was a significantly greater proportion of CD4+CD29+ T lymphocytes (29.3 +/- 6.1% and 31.1 +/- 9.0%; P less than 0.05) with concomitant diminution of CD4+CD45RA+ T lymphocytes (8.3 +/- 3.3% and 11.4 +/- 1.5%; P less than 0.01) in patients infected with HTLV-I or HTLV-II respectively, when compared with controls. The increased percentage of CD4+CD29+ subpopulations showed a direct correlation (rs = 0.86; P less than 0.001) with HTLV-specific antibody production. No difference in the CD8 population coexpressing CD29 and S6F1 (an epitope of LFA-1) were observed in the HTLV-infected group when compared with normal donors and functional analysis exhibited minimal cytotoxicity against lectin labelled heterologous target cells. Thus, the shift in the suppressor/cytotoxic to helper/inducer 'memory' CD4+ may be associated with immunoregulatory abnormalities often found in persons infected with HTLV-I or HTLV-II.

Antigens, CD↗