The skin homing receptor cutaneous leucocyte-associated antigen (CLA) is up-regulated by Leishmania antigens in T lymphocytes during active cutaneous leishmaniasis.

The cutaneous leucocyte-associated antigen receptor (CLA) can direct Leishmania-specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte-associated antigen 1 (LFA-1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A-CL) presented lower levels of T lymphocytes expressing the CLA(+) phenotype (T CD4(+) = 10.4% +/- 7.5% and T CD8(+) = 5.8% +/- 3.4%) than did healthy subjects (HS) (T CD4(+) = 19.3% +/- 13.1% and T CD8(+) = 21.6% +/- 8.8%), notably in T CD8(+) (P < 0.001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up-regulated CLA in T cells (CLA(+) in T CD4(+) = 33.3% +/- 14.1%; CLA(+) in T CD8(+) = 22.4% +/- 9.4%) from A-CL but not from HS. An enrichment of CLA(+) cells was observed in lesions (CLA(+) in T CD4(+) = 45.9% +/- 22.5%; CLA(+) in T CD8(+) = 46.4% +/- 16.1%) in comparison with blood (CLA(+) in T CD4(+) = 10.4% +/- 7.5%; CLA(+) in T CD8(+) = 5.8% +/- 3.4%). Conversely, LFA-1 was highly expressed in CD8(+) T cells and augmented in CD4(+) T from peripheral blood of A-CL patients. In contrast, CD62L was not affected. These results suggest that Leishmania antigens can modulate molecules responsible for migration to skin lesions, potentially influencing the cell composition of inflammatory infiltrate of leishmaniasis or even the severity of the disease.

Increased adhesive properties of eosinophils in sickle cell disease.

OBJECTIVE: A role for leukocytes in vasoocclusion is becoming increasingly recognized. Here we investigate a possible role for the eosinophil in sickle cell anemia (SCA). PATIENTS AND METHODS: Eosinophils were isolated from whole blood samples of 59 steady-state SCA homozygous SS and control individuals using Percoll gradient separation, followed by immunomagnetic sorting. Adhesion of cells to FN was evaluated using static adhesion assays (60 min, 37 degrees C, 5% CO2) and eosinophil adhesion molecular expression was observed by flow cytometry. RESULTS: SCA patients presented significantly elevated absolute eosinophil numbers. Furthermore, eosinophils isolated from these individuals demonstrated a significantly greater adhesion ( approximately 70% increased) to fibronectin (FN) than normal eosinophils in static adhesion assays. Coincubation of eosinophils with integrin-blocking monoclonal antibodies in adhesion assays showed that an association of the VLA-4, LFA-1, and Mac-1 integrins mediate the adhesion of SCA eosinophils to FN. Flow cytometry demonstrated that the expression of these integrins, however, was unaltered on the surface of SCA eosinophils, suggesting that the increased SCA eosinophil adhesion is a consequence of increased integrin affinity or avidity. SCA eosinophil adhesion to FN was further increased by the cytokine, GM-CSF, indicating that inflammation processes may further stimulate eosinophil adhesion in these patients. CONCLUSION: We report that eosinophil numbers may be significantly increased in SCA individuals and that these cells appear to exist in an activated state. Such alterations may indicate a role for the eosinophil in the vasooclusive process.

Oral lichen planus: immunohistology of mucosal lesions.

BACKGROUND: Current evidence suggests that immunological mechanisms are involved in oral lichen planus (OLP) pathogenesis. The events implicate activated epithelia that comprise antigen-presenting Langerhans cells, immunocompetent keratinocytes and subepithelial inflammatory infiltrate. Also, the presence of a high density of leucocyte cells may occur for the expression of a variety of adhesion molecules. The aim of this study was to analyse the immunoexpression of some adhesion molecules as well as lymphocytic markers in order to determine the disease pathogenesis in a Venezuelan population. METHODS: The 18 OLP and 10 normal oral mucosa biopsies were immunostained for CD4, CD8, CD1a, LFA-1, VCAM-1 and ICAM-1. RESULTS: The results showed an increased number of CD4+, CD8+, CD1a+ cells in OLP. Serial sections showed CD4+ and CD8+ cells also expressed LFA-1. The expression of ICAM-1 and VCAM-1 were significantly higher in OLP. CONCLUSIONS: The immunological reaction begins with Langerhans cells activation, which presents an antigen to CD4+ lymphocytes. Those cells through ICAM-1 and LFA-1 promote epithelial destruction. Afterwards, cytokine production, ICAM-1 and VCAM-1 expression can activate CD8+ lymphocytes leading to the chronic form of the disease.

Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules.

The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium of Trypanosoma cruzi-infected patients and experimental animals are undefined. Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma-induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1-alpha, were found to be the dominant cytokines expressed in situ during acute and chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was only detected during the chronic phase. Altogether, the results indicate that the distribution of T-cell subsets in the myocardium of T. cruzi-infected mice reflects the particular profile of adhesion molecules acquired by most peripheral CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma-inducible molecules present in the inflamed tissue contribute to the establishment and maintenance of T. cruzi-induced myocarditis.

Expression of adhesion molecules in poststreptococcal glomerulonephritis.

Because adhesion properties of leukocytes are important for the influx and localization of leukocytes in sites of inflammation, we studied, the expression of intercellular adhesion molecule 1 (ICAM-1), lymphocyte-function-associated antigen 1 (LFA-1), vascular cell adhesion molecule- 1 (VCAM-1) and CD 11b in 14 kidney biopsies of PSGN patients, arbitrarily divided into early biopsies (less than 15 days after onset of PSGN) and late biopsies (17-90 days). In PSGN, intraglomerular ICAM-1 expression was increased in early biopsies (score 3.1 +/- SEM 0.2; P < 0.005) and decreased with time; in late biopsies the score (2.0 +/- 0.2) was similar to that of normal kidney (1.3 +/- 0.3). In the interstitium ICAM-1 was increased (early PSGN = 836 +/- 56 positive cells/mm2, late = 552 +/- 60.0; versus normal = 364 +/- 12.4; P < 0.05). LFA-1 expressing cells in glomeruli were also increased in early biopsies (10.0 +/- 2.1 positive cells per glomerular cross-section (gcs), versus normal 2.9 +/- 1.4; P < 0.05). In the interstitium, LFA-1 positive cells were increased (early PSGN = 221 +/- 79.6 cells/mm2, late PSGN = 134.5 +/- 45.1, normal = 21 +/- 8.7; P < 0.05). VCAM-1 in glomeruli and interstitium was not increased in PSGN. Our studies demonstrate increased expression of adhesion molecules ICAM-1 and LFA-1 in the kidney of PSGN patients, and these findings were more pronounced in early biopsies; adhesion molecules are probably involved in the inflammatory infiltration of this disease.

Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic Chagas' disease.

We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.

Expression of ICAM-1 (CD54) on normal and leukaemic B cells: implication for the mixed lymphocyte reaction.

Peripheral blood normal B lymphocytes were found to be poor stimulators in the mixed lymphocyte reaction (MLR), in contrast to normal activated B cells which were strong stimulators. This increased capacity to stimulate a strong MLR correlated with an increased expression of the ICAM-1 (CD54) molecule on the surface of these cells. Similarly, the capacity of leukaemic B cells to induce an allogenic stimulation in the MLR was limited to the ICAM-1 (CD54) positive leukaemic cells. The ability of normal activated or leukaemic B cells to induce an MLR was blocked by antibodies directed against ICAM-1.