Modulation of Contact Sensitivity Responses by Bacterial Superantigen

Joachim Saloga, Alexander H. Enk, Detlef Becker, Mansour Mohamadzadeh, Stefanie Spieles, Iris Bellinghausen, Donald Y.M. Leung, Erwin W. Gelfand, Jürgen Knop
1995 Journal of Investigative Dermatology  
Superantigens are potent modulators of the immune system, especially T cells. Therefore, we determined the influence of superantigens on the T -cell-mediated immune response, contact sensitivity. We chose the combination of staphylococcal enterotoxin B (SEB) as superantigen and 2,4-dinitrofluorbenzene (DNFB) as the contact sensitizer, because in BALB/c mice SEB reacts almost exclusively with V/38+ T cells, and these cells are capable of transferring contact sensitivity to DNFB from sensitized
more » ... nors to naive syngeneic recipients. Pretreatment with a single intradermal injection of 50 ng SEB 24 h before DNFB exposure at the same site on the lower abdomen enhanced the induction of contact sensitivity: its intradermal injec#on permitted sensitization with C ontact. all ergic responses as a manifestation .of. delayed-type hypersensitivity arc mediated by T cell s [1, 2] . During th e induction phase, antigen/ h aptenspecific T cells are induced by appropriate presentation of the hapten in the context of major histocompatibility co mplex (MHC) class II molecules. Inappropriate presentation, however, leads to anergy and tolerance due to the lack or presence of soluble or m e mbrane-bound factors [3, 4] . Stimulation ofT cells can also occur in the presence of supera n tigens that bind to the V {3-region of the af3 T -cell receptor [5, 6] and to MHC-class TI molecules outside the regular antigen binding groove [7 ,8]. This interaction can .l ead to activation, cytokine production, and proliferation or to anergy and deletion of the responsive Vf3 T-cell subsets [9-1.7]. In view of its broad effects on T-ccU responses, we evalu ated the effect of a superantigen on the development of contact sensitivity. Because of potential clinical significan ce, we chose a bacterial superantigen derived from bacteria that colonize the skin in various disease co nditio n s, as such supcrantigeni c products may very well influence contact dermatitis reactions in a clinical setting [18, 19] . Staphylococcal enterotoxins (SE) have been sh own by other investigators to suppress delayed-type hypersensitivity -~~sponses as Manuscript . P...eprint requests to: Dr. Joa chim Sa.loga, Universitat-1-lautkLinik, Langenbeckstrasse 1. 55'131 Main z, Gemumy. Abbreviations: CS, contact sensitivity; LN. lymph nodc(s); SALT, skinassociated lymphoid tissue; SE, staphylococcal enterotoxin. non-sensitizing concentrations of DNFB as assessed by ear swelling responses after challenge with DNFB. In contrast, pretreatment with repeated intradermal injections of 50 ng SEB every other day over at least 1 week inhibited the induction of contact sensitivity following sensitization. The enhancing effect of SEB may be explained by the creation of a proinflammatory milieu in the skin after a single intradermal injection o£ the bacterial toxin, whereas the inhibitory effect may be due to tolerization of V/38+ T cells. The data indicate that products of skin-colonizing bacteria that can serve as superantigens are able to augment or inhibit the developement of contact sensitivity. Key words: cor1tact settsitivity!Sitperatttigert!staphylococcal et~terotoxirt B/2,4-dittitro.fluorbenzet~e. J l1west Dermatol 105: [220][221][222][223][224] 1995 well as other immun e reactions in IJiiJo [20 -23] , but true contact sen sitivity was not investigated in these studi es. Inhibition of contact sensitivity to 2,4-dinitroAu o rb e n zene (DNFB) has b een desc1·ibed in only one investigation u sin g C57BL/6 mice utilizing SEA as a superantigen [24] , but no ana lys is ofVf3 T-cell populations was included in tlus study. In tl1e present study we c hose the combination of DNFB and SEB, as contact sensitivity to DNFB is a well-characterized model, and Vf38 + T ce Lls are capab le of transferring contact sensitivity to thjs hap ten in BALB/c mice. In BALB/c mice Vf38 + T cells represent a large T -cell population and are the primary responders to SEB [7]. MATEIUALS AND METHODS Experimental Animals Female BALB/c mice Qackson Laboratories, Bar Harbor, M:E) of about 10 weeks of age and majntained under approved instimtional guidelin es were used in all experiments. T hese mjce lack Vf33and V{317-positive T cell s. Therefore V{37 (sma ll fraction) and V{38 (m,\ior proportion) serve as the SEE-reactive T cells (7]. Contact Sensitization Unless otherwise indi cated the lower abdomen was shaved with an electric clipper and pajnted on two consecutive days with 30 J.Ll of DNFB (Sigma, St. Louis, MO) dissolved in oil/acetone (mixture of 1:4 parts) at a concentration of 0.5'Yu. Control animals were painted with the solvent oil/aceton e alone. Testing for Contact Sensitivity After measurement of the baseline thickness of both ears, 30 J.LI of DNF.B 0.2'!1" dissolved in oil/acetone (mixture of l :4 parts), was applied onto the dorsum of both ears, and ear thickness was measured with a modified micrometer 24 h later. The car swelling response was calcul ated by subtracting the thickness prior to testing 0022-202X/95/S09.50 • SSD I0022-202X(95)00229-E •
doi:10.1111/1523-1747.ep12317503 pmid:7636304 fatcat:ew2bwn4b4fdhzlbzdycvzlnw3e