INFLUENCE OF DOSE AND ROUTE OF ANTIGEN INJECTION ON THE IMMUNOLOGICAL INDUCTION OF T CELLS

doi:10.1084/jem.139.3.528

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ARTICLE

INFLUENCE OF DOSE AND ROUTE OF ANTIGEN INJECTION ON THE IMMUNOLOGICAL INDUCTION OF T CELLS

P. H. Lagrange ¹, G. B. Mackaness ¹, and T. E. Miller ¹

¹ From the Trudeau Institute, Saranac Lake, New York 12983

Delayed-type hypersensitivity (DTH) develops in the absenceof an adjuvant when mice are injected intravenously or subcutaneouslywith an appropriate dose of sheep red blood cells (SRBC). Theoptimal intravenous dose of 10⁵ SRBC (in CD-1 mice) producesmaximum DTH which decays exponentially from its peak on day4. Increasing the dose of SRBC reduces and eventually abolishesall evidence of DTH. DTH fails to reappear in respose to secondarystimulation except in splenectomized mice in whom the developmentof DTH is not suppressed, even by massive doses of SRBC. Hencethe suppression cannot be due to antigen as such.

The optimaldose of SRBC for sensitization by footpad inoculation is 100-foldhigher (10⁷ SRBC in CD-1 mice), but even 10⁹ SRBC do not blockthe induction of DTH by this route of immunization. A blockingdose of SRBC, given intravenously 1 day before footpad inoculation,completely suppresses cell proliferation in the draining lymphnode, prevents PFC production there, and blocks the inductionof DTH by a sensitizing dose of SRBC. If given 1 day after footpadsensitization, intravenous antigen has little effect on thecellular response in the regional node but DTH is still completelysuppressed. Blocking of induction and expression may depend,therefore, on different mechanisms.

Submitted on October 25, 1973

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