ARTICLE
Auteur(s) :, Laura Lacueva, Antonio Guilabert, Juan Ferrando*
Department of dermatology, Hospital Clínic, Villarroel, 170,
08036-Barcelona (Spain)
Sir,We have read with interest the article by Santamaria-Babí [1]
on CLA+ T cells in cutaneous diseases. We would like to provide new
data from our research experience about the expression of cutaneous
lymphocyte-associated antigen (CLA) in alopecia areata.We initially
demonstrated that inflammatory infiltrates from alopecia areata
plaques express CLA at an overall rate nearly six times greater
than healthy controls (p = 0.004). Moreover, we found significant
differences when CLA expression was analyzed by anatomic area of
the hair follicle (intraepidermic, intrafollicular, perifollicular
and perivascular expression) (table 1)( Table
1 )[2].In a subsequent work [3], we observed that not only
T-lymphocytes but also every type of cell composing the
inflammatory infiltrate of alopecia areata, showed an increased
expression of CLA as compared to healthy controls.We obtained 12
biopsies from alopecic plaques of patients with alopecia areata and
8 biopsies from the scalp of healthy controls. CLA expression of
the cutaneous infiltrate was determined by means of double direct
immunoflorescence with primary monoclonal antibodies anti-CD1a,
anti-CD4, anti-CD8, anti-CD68 and HECA-452 and secondary
fluorescent antibodies against IgG and IgM using the double
staining technique with FITC and rodamine. Samples were analyzed
with a confocal microscope at x40 magnification. A representative
field was selected, photographed and digitally stored. CLA+ cells
with visible nuclei were strictly counted.The majority of T-cells
expressed CLA (CD4+ T-cells = 71% and CD8+ T-cell = 70%). In
addition, 33% of CD1a+ Langerhans cells were positive for CLA
staining. Finally, CD68+ macrophages achieved the lowest CLA
expression rate (20%) (table 2)( Table 2
).We also analyzed the CLA expression of these cells in the
aforementioned anatomic sites of the hair follicle. Of note, the
majority of T-cells in the perifollicular area were CLA+. We also
found that the CLA expression rate of Langherhans cells was higher
in the perifollicular area (56% vs. 21% in the intrafollicular
area).The CLA is a surface-cell glycoprotein which plays a crucial
role in the migration of circulating T-cells to the skin.
E-selectin (an adhesion molecule expressed by endothelial cells
under inflammatory stimuli) is the ligand for CLA. The expression
of CLA is tissue-specific and takes place on T-cells undergoing
naive (CD45RA+) to memory transition
(CD45RO+) in the lymph nodes of the skin. Two enzymes
[α1,3-fucosyltranferases IV and VII (FucTIV and FucTVII)] have been
characterized as the main regulators of the expression of CLA.
IL-12 upregulates the expression of CLA since this cytokine induces
the synthesis of FucTVII on T-cells undergoing naive to memory
transition. Conversely IL-4 downregulates the expression of CLA due
to inhibition of FucTVII expression [1].In alopecia areata, there
might be other markers with a function similar to CLA, which allow
the adherence and rolling of T-cells along the vascular
endothelium, and ultimately the extravasation of such cells towards
the skin. Of interest, Wagner et al. [4] detected a predominant
expression of the splice variant 10 of CD44 (CD44v10) (a receptor
involved in the process of leukocyte homing in the skin) on T-cells
in lesional alopecia areata skin. Furthermore, Freyschmidt-Paul et
al. [5] observed that mice grafted with lesional alopecia areata
mouse skin and injected with the murine CD44v10-neutralizing
antibody, developed alopecia areata to a much lesser degree than
those grafted mice injected with anti-CD44 standard or
phosphate-buffered saline only, suggesting an essential role of
CD44v10 in the migration of T-cells to the affected skin of
patients with alopecia areata.
References
1 Santamaría-Babí LF. CLA+ T cells in cutaneous diseases. Eur
J Dermatol 2004; 14: 13-8.
2 Lacueva L, Hausmann G, Ferrando J. Expresión
del antígeno linfocitario cutáneo en las placas alopécicas de
pacientes con alopecia areata. Med Cutan Iber Lat Am 2003; 31:
161-72.
3 Lacueva L, Hausmann G, Ferrando J. Expresión
del antígeno linfocitario cutáneo y de la E-selectina en la
alopecia areata. Med Cutan Iber Lat Am 2003; 31: 295-303.
4 Wagner SN, Wagner C, Reinhold U, Funk R,
Zoller M, Goos M. J Invest Dermatol 1998; 111:
464-71.
5 Freyschmidt-Paul P, Seiter S, Zoller M,
Konig A, Ziegler A, Sundberg JP, et al. J
Invest Dermatol 2000; 115: 653-7.
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