Peripheral Langerhans Cells Research Articles

Observation of Corneal Langerhans Cells by In Vivo Confocal Microscopy in Thyroid-Associated Ophthalmopathy

ABSTRACT Purpose: To examine the density and morphology of Langerhans cells (LCs) in the cornea of patients with thyroid-associated ophthalmopathy (TAO). Methods: Forty patients with TAO and 20 healthy volunteers were studied. All subjects underwent a thorough ophthalmic examination of both eyes. The ocular surface status was assessed by Ocular Surface Disease Index (OSDI) symptom questionnaires, tear break-up time (BUT), fluorescein staining and the Schirmer test. Laser scanning in vivo confocal microscopy was applied to evaluate the LC density and morphology in both central and peripheral cornea. The correlations between confocal microscopy data and clinical data were also analyzed. Results: The OSDI and fluorescein staining values were significantly higher, while BUT and Schirmer test scores were lower in both active and inactive TAO patients compared to the controls. Central LC densities of patients with active TAO (76.38 ± 67.77 cell/mm2) and inactive TAO (47.49 ± 38.58 cell/mm2) were both significantly higher than those of the controls (21.46 ± 21.74 cell/mm2). The number of LCs in the peripheral cornea was also significantly increased in the active TAO group (131.53 ± 74.18 cell/mm2) compared to the control group (70.21 ± 37.76 cell/mm2). Central LC morphology (LCM) values were significantly higher in both active (1.77 ± 0.63) and inactive (1.51 ± 0.63) TAO groups compared to the control group (1.01 ± 0.80), whereas peripheral LCM scores of the two TAO groups were increased without statistical significance. There were significant correlations between both central LC density and central LCM scores and clinical data, including clinical activity score, OSDI and Schirmer test scores, and between peripheral LC density and OSDI and Schirmer test scores. No significant correlations were found between peripheral LCM scores and clinical data. Conclusions: The increase of corneal LCs in density and maturation in patients with TAO reflects an activated state of the local immune system, which indicates an inflammatory process in the cornea of TAO.

Dry eye and corneal langerhans cells in systemic lupus erythematosus.

Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye.

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis

APCs of the ocular surface, including corneal Langerhans cells (LCs), offer the opportunity to gain insight into the activity of innate immunity. We examined corneal LCs and dry eye parameters in ankylosing spondylitis (AS). Twenty-four AS patients with varying degrees of disease activity and 24 healthy participants were enrolled. Central and peripheral LC numbers, and Langerhans cell morphology (LCM) were assessed with invivo laser confocal microscopy. In addition, ocular surface disease index, lid parallel conjunctival folds, tear break up time, and Schirmer test were evaluated. LC densities and central LCM were greater in AS patients than in the controls. Moreover, LCM was significantly greater in patients with higher systemic inflammation according to elevated C-reactive protein (CRP). Also, tear production was greatly suppressed in patients with more severe onset of the systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index and elevated CRP. Greater corneal LC density and LCM in AS may reflect an increased activation state of the innate immune system of the cornea in AS, which correlates with the systemic activity of AS even without ocular symptoms. Nonetheless, higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis

AbstractPurpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters and disease activity in ankylosing spondylitis(AS).Methods Twenty four AS patients (mean age: 41.8±9.8 years) with various degree of disease activity and twenty four healthy subjects (mean age: 47.9 ± 16.4 years) were enrolled. Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), and Schirmer test (ST) were evaluated. In addition, central and peripheral LCs numbers and Langerhans cell morphology (LCM) were assessed with in vivo laser confocal microscopy.Results Tear production was greatly suppressed in patients with more severe systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C‐reactive protein (CRP) (BASDAI≤4.0 vs BASDAI>4.0 10.2±8.5 vs 4.0±5.3; CRP≤5.0 vs CRP>5.0 17.2±4.2 vs 3.9±5.5 p<0.05 for all). LCs densities and central LCM were greater in AS patients than in the controls (LC density: 77.5±44.9 vs 23.8±33.8 and central LCM: 1.7±0.7 vs 0.95±0.75 p<0.05 for all).Conclusion Greater corneal LC density and LCM may reflect an increased activation of the corneal innate immune system, which correlates with the systemic activity of AS even without ocular symptoms. Higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.

In vivoconfocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis

Corneal Langerhans cells (LCs) offer the opportunity to gain insight into the activity of the innate immunity. We examined the density and the distribution of LCs and compared the results with dry-eye parameters in rheumatoid arthritis (RA). Fifty-two RA patients with various degrees of disease activity and 24 healthy subjects were enrolled. Peripheral and central LC number and morphology were assessed with invivo laser confocal microscopy. In addition, ocular surface disease index (OSDI), lid parallel conjunctival folds, Schirmer test, and tear break-up time (TBUT) were evaluated. The prevalence of central and peripheral LC, and the central LC morphology values (LCM) were higher than normal in RA. Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti-TNF or glucocorticosteroid (GCS) therapy exhibited normal LCM, and normal central and peripheral LC density. OSDI was higher and TBUT was lower than normal in RA. The alteration of LC in RA suggests an active inflammatory process in the cornea, which may reflect an increased activation state of the innate immune system-even in inactive stages of RA and without ocular symptoms. The results also indicate ocular effects of GCS therapy in RA.

In vivo confocal microscopic examination of corneal Langerhans cell density, distribution and evaluation of dry eye in rheumatoid arthritis

AbstractPurpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters in rheumatoid arthritis (RA).Methods 52 RA patients (mean age: 58 [49‐66]) with various degree of disease activity and 24 healthy subjects (mean age: 61 [52.5‐67]) were enrolled. Central and peripheral LC number and morphology were assessed with in vivo confocal laser corneal microscopy. In addition, lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), Schirmer’s‐test (ST), and ocular surface disease index (OSDI) were also evaluated. .Results The prevalence of central and peripheral LCs and the central LC morphology values (LCM) were higher in RA compared to controls (median [interquartile range]: 42.50 [22.95‐93.50] vs 10.00 [0.00‐42.33] cell/mm2, 98.00 [62.00‐154.5] vs 59.50 [45.25‐94.75] cell/mm2, and 2.00 [1.00‐2.00] vs 1.00 [0.25‐1.00], respectively, p<0.05 for all). Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti‐TNF or corticosteroid therapy exhibited LCM and central and peripheral LC density comparable to controls. TBUT values were lower and OSDI scores were higher in RA than in controls (9.00 [7.00‐12.00] vs 12.00[9.00‐14.00] seconds and 20.00 [10.93‐38.21] vs 9.75 [4.93‐16.28], respectively, p<0.05 for all). ST results were comparable in RA and controls.Conclusion Dendritic cell accumulation and maturation in the corneal center suggest the involvement of the cornea in RA, even in patients in inactive stage and without ocular symptoms.

Effect of cytokine-induced migration of Langerhans cells on corneal allograft survival.

The unique paucity of Ia+ Langerhans cells (LCs) in the central cornea contributes to the immunological privilege of corneal allografts. A variety of stimuli can induce the centripetal migration of peripheral LCs. At least one of these stimuli (i.e. latex bead instillation) induces interleukin-1 (IL-1) secretion by corneal cells which acts as a potent chemoattractant for LCs. Within 30 minutes of intracorneal injection of IL-1, centripetal migration of LCs can be detected. The presence of donor-derived LCs in corneal allografts doubles the incidence of rejection of fully allogeneic corneal allografts as well as MHC matched, multiple minor H mismatched corneal allografts. Although the presence of donor-specific LCs greatly jeopardises corneal allograft survival, migration of host-derived LCs into corneal allografts does not appear to increase the risk of rejection.

HLA-D/DR restriction of Langerhans cell-dependent antigen activation of T lymphocytes. The same D/DR determinants are restriction elements on monocytes and Langerhans cells.

In previous studies we have shown that the response of T cells to antigen presented by epidermal Langerhans cells (LC) is restricted by products of the HLA-D region. An optimal antigen-specific response required that the LC used for antigen presentation shared both, or at least one, of the D/DR determinants of the T-cell donor. These studies were, however, disturbed by a strong allogeneic response induced by the foreign D/DR determinants of the LC. We report here that by separating the antigen-specific T cells from those that are alloreactive, a clearer picture of the D/DR restriction phenomenon may be obtained. Furthermore, the present studies demonstrate that the same D/DR determinants function as restriction elements on peripheral blood monocytes and LC.