Suppression of In Vitro Lymphocyte Transformation During an Experimental Dermatophyte Infection

Abstract

During primary Trichophyton mentagrophytes infection of strain 2 guinea pigs, the colony-forming units (CFU) of fungi present within the lesion peaked between days 7 and 14, whereas the severity of the lesion itself peaked between days 11 and 16. Concomitant with the latter peak, a pronounced depression in the in vitro mitogenic activity of spleen cells (SPC) and lymph node cells (LNC) was observed. Only after resolution of the primary infection (day 21) did LNC show increased deoxyribonucleic acid (DNA) synthesis in the presence of fungal antigens. During cutaneous reinfection, there was no distinct peak fungal load and CFU appeared to decrease steadily during the accelerated course of a reinfection disease. LNC from guinea pigs with severe, ulcerated reinfection lesions generally exhibited a heightened response to fungal antigen in vitro. LNC from guinea pigs with mild reinfection dermatophytosis had depressed in vitro reactivity to mitogens and dermatophyte antigen. The suppression of blastogenic activity during dermatophyte infection appeared to be associated with autologous serum components, since increased DNA synthesis resulted when SPC or LNC were cultured with fetal calf serum. The depressed in vitro DNA synthesis of lymphocytes (cultured with dermatophyte antigens) that were harvested during reinfection was not accompanied by an impaired ability of infected guinea pigs to respond with a delayed-type hypersensitivity skin test in vivo. These results support the hypothesis that experimental T. mentagrophytes dermatophytosis is a cell-mediated hypersensitivity disease that can be modified by immunosuppressive control mechanisms elaborated or induced by the fungus.

Cutaneous defenses against dermatophytes and yeasts

“…Suppression of lymphocyte blastogenic responses has been related to potentially immunosuppressive serum factors in acute Trichophyton mentagrophytes infections produced experimentally in animals (37,102). Studies with human patients also suggest that serum factors may be involved in suppression of cell-mediated immunity to fungal antigens in chronic dermatophytosis (39,229,278).…”

Cell mediated cross-reactivity in vivo and in vitro to purified dermatophyte antigen preparations in sensitized guinea pigs

“…macrophages, or a suppressive factor released by these cells. It has recently been demonstrated that guinea pigs with experimental dermatophyte infection have inhibit ing serum factors that depress blastogenic activity (6). It is possible that such factors are also present in dermatophyte-immunized animals.…”

Recombinant expression and antigenic properties of a 31.5-kDa keratinolytic subtilisin-like serine protease fromMicrosporum canis

“…In the control guinea pigs, the lymphocyte responses remained at a basal level throughout the experiment (data not shown). Other authors working on other dermatophytes and using crude, non‐purified antigens, observed in experimentally infected guinea pigs [22] and mice [23] a suppression of lymphocyte reactivity to T‐ and B‐cell mitogens when cutaneous lesions were maximal. They attributed this suppression to induction of T‐suppressor cell activity [23] and/or a host or fungal serum suppressor factor [22].…”

“…Other authors working on other dermatophytes and using crude, non‐purified antigens, observed in experimentally infected guinea pigs [22] and mice [23] a suppression of lymphocyte reactivity to T‐ and B‐cell mitogens when cutaneous lesions were maximal. They attributed this suppression to induction of T‐suppressor cell activity [23] and/or a host or fungal serum suppressor factor [22]. In this study, there was no evidence of non‐specific suppression of responses to the mitogen ConA (Table 1), although the possibility of a serum‐suppressive factor could not be excluded, as horse serum rather than contemporary autologous serum was used.…”