The lymphoid cells responsible for protective immunity to histoplasmosis were characterized. Adoptive transfer of spleen and peritoneal cells treated with antiserum to theta-antigen from mice immunized with ribosomes or live yeast cells of Histoplasma capsulatum abrogated the ability of these cells to protect the syngeneic recipients, whereas treatment of lymphoid cells with antiserum to IgG did not affect the immunity. Prior removal of glass-adhering cells from spleen and peritoneal cell suspensions did not alter their protective activity. Treatment with mitomycin C, an antimitotic agent, ablated the capacity of immune lymphocytes to protect the syngeneic recipients. These results indicate that the immune spleen and peritoneal cells that confer immunity to histoplasmosis are thymus-dependent (T) lymphocytes and that their active proliferation in the recipients is necessary for expression of the protective immunity. Furthermore, the immunity elicited by immunization with histoplasma ribosomes and live yeast cells is mediated by a similar mechanism.

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This investigation was designed to compare the role of lymphoid cells and immune serum in protective immunity induced by immunization with ribosomes or live yeast cells of Histoplasma capsulatum. Spleen cells, peritoneal cells, and serum from CH mice immunized with Histoplasma ribosomes or live cells were transferred intravenously to separate groups of syngeneic recipients. All recipients along with a set of immunized and control mice were challenged intravenously with 4 x 106 yeast cells of H. capsulatum, and protection was assessed. Immunization with ribosomes or live cells provided 90 to 100% protection. Mice receiving filtered spleen cells or peritoneal cells from donors immunized with live cells showed 90 to 100% protection; 80 to 90% protection was observed for mice receiving cells from ribosome-immunized donors. In contrast, no evidence of protection was seen in mice receiving serum from either live-cellor ribosome-immunized mice. Peritoneal cells were far more efficient than spleen cells in adoptive transfer of immunity. The adoptive immunity in recipients persisted for at least 3 weeks after transfer, the longest period tested in the present study. These results indicate that the immunity elicited by immunization with Histoplasma ribosomes or live cells is mediated by a cellular mechanism.

Summary: We studied the relationship between protective immunity and delayed hypersensitivity (DH) in mice immunized by s.c. inoculations with 105 live yeast cells of H. capsulatum. At 1 to 105 days post‐immunization, immune splenocytes were transferred to syngeneic recipients. Immunized donors and recipients of immune splenocytes showed significant footpad reactivity to histoplasmin and Histoplasma ribosomes at 4 days (p < 0.001), which peaked between 21 and 28 days (p < 0.001) and thereafter showed a gradual decline reaching the control level at 105 days. A significant inhibition of macrophage migration was observed in peritoneal exudate cells from both donors and recipients at 4 days (p < 0.001); it remained almost at the same level until 43 days but was reduced at 63 days (p < 0.01). Immunized mice were protected against a lethal challenge with Histoplasma from day 7 onward. Adoptive transfer of splenocytes conferred 90 to 100% protection to recipients when the cells were obtained 14 to 105 days after immunization, but protection, was not transferred with spleen cells taken 4 to 7 days post‐immunization. The results indicate that the development of DH proceeds the expression of protective immunity to histoplasmosis in mice and the immunity persists longer than the DH reactions after a single immunizing dose. Zusammenfassung: Wir untersuchten die Beziehungen zwischen protektiver Immunität und der Überempfindlichkeit vom verzögerten Typ (DH) in Mäusen, die subkutan mit 105 lebenden Histoplasma capsulatum‐Zellen in der Hefephase infiziert worden waren. Vom 1. bis zum 105. Tag nach der Immunisierung wurden Splenozyten auf syngenische Empfängertiere Übertragen. Die immunisierten Spender und die Empfänger immuner Splenozyten zeigten eine signifikante Pfo‐ten‐Reaktivität gegenfiber Histoplasmin und Histoplasma‐Ribosomen vom 4. Tag an; die Reaktion erreichte zwischen dem 21. und dem 28. Tag ihren Höhepunkt (p < 0,001), nahm danach wieder ab und war am 105. Tag kontrollgleich. In Peritonealexsudatzellen (PEC) sowohl der Spender‐ als auch der Empfángertiere wurde eine signiflkante Hemmung der Makrophagen‐Migration vom 4. Tag an beobachtet (p < 0,001), die etwa 42 Tage lang auf dem gleichen Niveau blieb, am 63. Tag aber reduziert war (p < 0,01). Die immunisierten Mäuse waren vom 7. Tag an gegenÜber einer letalen Histoplasma‐Infektion geschÜtzt. Die Übertragung von Splenozyten fÜhrte zu einem 90 bis 100%igen Schutz der Emprángertiere, wenn die Zellen 14 bis 105 Tage nach der Immunisierung gewonnen worden waren; die Immunität konnte jedoch nicht mit Splenozyten, gewonnen 4 bis 7 Tage nach der Immunisierung, Übertragen werden. Die Ergebnisse belegen, daß die Entwikklung der Überempfindlichkeit vom verzögerten Typ in Mäusen der Expression protektiver Anti‐Histoplasma‐Immunität vorausgeht und daß nach einem einzigen Inununisierungsschritt die Immunität länger anhält, als die Überempfindlichkeit vom verzögerten Typ.