Modulation of cellular immune responses in mice with disseminated histoplasmosis by recombinant interleukin-2.
Depression of the cellular immune responses in mice with disseminated histoplasmosis is associated with deficient production of interleukin-2 (IL-2) by splenocytes. Therefore, we examined whether a highly purified preparation of IL-2, recombinant human IL-2 (rIL-2), could modify the cellular immune responses in infected mice and whether this lymphokine could alter the severity of histoplasmosis in animals. Exogenous rIL-2, at concentrations of up to 1,000 U/ml, failed to augment the proliferative responses to concanavalin A by unfractionated splenocytes or splenic T cells from mice infected for 1 week. In addition, rIL-2 did not modulate the plaque-forming cell response to sheep erythrocytes by splenocytes from these same mice. However, at week 3, rIL-2 in concentrations ranging from 10 to 1,000 U/ml considerably augmented the proliferative response to concanavalin A and plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice. Kinetics studies demonstrated that rIL-2 exerted maximal immunoregulatory activity when added on day 0 or 1 to cultures of splenocytes. In vivo administration of rIL-2, 200 to 20,000 U/day, for 10 days to normal and 3-week-infected mice did not alter the proliferative activity of splenocytes to concanavalin A; 200,000 U of rIL-2 per day actually depressed the proliferative responses of splenocytes from normal and infected mice. In vivo, rIL-2 did not modify delayed-type hypersensitivity responses to sheep erythrocytes or to histoplasmin by normal and infected mice. Moreover, treatment with rIL-2 in vivo did not reduce the number of Histoplasma CFU in spleens of mice. Thus, despite the immunoenhancing effect of rIL-2 in vitro, this lymphokine failed to exert similar effects in vivo.
D000818:Animals; D002478:Cells, Cultured; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D007376:Interleukin-2; D011994:Recombinant Proteins