RESPONSES OF T-LYMPHOCYTES AND B-LYMPHOCYTES TO A PARACOCCIDIOIDES-BRASILIENSIS CELL-WALL EXTRACT IN HEALTHY SENSITIZED AND NONSENSITIZED SUBJECTS

Antigen-specific cellular immunity in paracoccidioidomycosis (PCM) has been poorly studied due to lack of standard in vitro lymphocyte proli feration assays. To standardize such an assay, we studied T and B cell responses to a Paracoccidioides brasiliensis cell wall extract (PbAg) in healthy subjects sensitized to either P. brasiliensis [Pb(+)Hc(-)] or to Histoplasma capsulatum [Hc(+)Pb(-)], and in nonsensitized perso ns. All subjects showed, as expected, a vigorous proliferative respons e to a control fungal antigen obtained from Candida albicans. Lymphocy tes from Pb(+)Hc(-) donors, but not from Pb(-)Hc(-) donors, reacted to PbAg by proliferating in a dose-dependent manner with a maximum react ion after 6-9 days, suggesting a secondary specific immune response. M ost activated cells were CD4+ lymphocytes. However Hc(+)Pb(-) donors' cells reacted with PbAg. Cross-reactivity with H. capsulatum was not u nexpected, since both fungi, but not C. albicans, share cell wall immu nogenic compounds. An enzyme-linked immunosorbent assay to detect huma n immunoglobulins (Ig) demonstrated that B cells from Pb(+)Hc(-) donor s, but not from Pb(-)Hc(-) ones, reacted with PbAg by secreting high l evels of IgG and IgM in 12-day culture supernatants. This secretion wa s possibly mediated by PbAg-activated CD4+ cells. We believe that anal ysis of T and B lymphocyte responses to PbAg will be useful in the inv estigation of the infection-associated immune impairment seen in some PCM patients.