Depression of Lymph Node Cell Proliferation Induced by Oxazolone

Abstract

The influence of topical exposure to two sensitizing chemicals on draining lymph node cell proliferative responses in BALB/c mice has been examined. Conventional contact sensitization with 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) has been shown to induce a rapid and systemic suppression of subsequent proliferative responses to topically applied chemical which can be adoptively transferred to recipient mice with immune lymph node cells. In contrast to some previous reports in which such suppression was found to be largely antigen-specific in nature, we report that, at least initially, the inhibition of lymphocyte proliferation induced by skin sensitization is hapten-non-specific. The relevance of this phenomenon to the regulation of contact sensitization is discussed.

Selective Impairment of T Lymphocyte Activation following Contact Sensitization with Oxazolone

“…Five days later, mice were challenged with oxazolone or vehicle on the dorsum of both ears and proliferative activity measured 3 days later. Stud ies with cultures of draining LNC revealed that, as previously reported [10], exposure to oxazolone at a distant site 5 days prior to challenge with the same chemical, resulted in a marked depression of chal lenge-induced proliferation ( fig. 2A).…”

“…It has been demonstrated previously that, in addi tion to inducing a vigorous primary proliferative re sponse in draining lymph nodes and the development of contact sensitization, topical exposure of mice to oxazolone results in the appearance of immunoregulatory mechanisms which serve to inhibit and con tain proliferative responses [10,11], These homeostatic mechanisms have the ability to influence both primary and secondary responses, and we speculate that their pyhsiological role is in preventing excessive lympho prolifération following the initial and subsequent ex posures to highly immunogenic antigen (such as ox azolone) [11]. The data contained within this report demonstrate that the active regulatory events which result from oxazolone sensitization and which influ ence LNC proliferation are selective for T lympho cytes.…”

“…The results of autoradiographic analyses provide additional evidence that the depres sion of lymphocyte proliferation during primary and secondary responses to oxazolone is T cell-selective. We have proposed elsewhere [10] that the decline in LNC hyperplasia recorded at periods of 3 or more days following primary exposure to oxazolone is at tributable to rapidly induced immunoregulation. It is of interest therefore that the frequency of proliferat ing cells in lymphoid follicles was beginning to in crease on the 6th day following exposure, when activ ity in T lymphocyte areas was declining.…”

“…In a previous study, it was found that topical expo sure of mice to oxazolone results in a depression of subsequent lymph node cell (LNC) proliferative re sponses to the same, and other, skin allergens [10], The inhibition of proliferation caused by oxazolone comprises both antigen-specific and non-antigen-spe cific mechanisms and is considered to play an impor tant role in the regulation of cutaneous sensitization [ 11].…”

Dendritic Cell Accumulation in Draining Lymph Nodes during the Induction Phase of Contact Allergy in Mice

“…The spontaneous proliferative activity of unfractionated drain ing LNC populations was measured as described previously [20], Briefly, unfractionated suspensions of LNC in RPMI-FCS were seeded into 96-well microtiter plates at a concentration of 2.5 x 106 cells/ml cultured for 24 h at 37°C in a humidified atmosphere of 5% C 0 2 in air with 2 pCi of 5H-methyl thymidine (specific activity 2.5 Ci/mmol; Amersham International, Amersham, UK). Culture was terminated by automatic cell harvesting and 'H-TdR incorpor ation determined by f)-scintillation counting.…”