Using guinea pigs of strains 2 and 13 and their F1 hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant.
(a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable.
(b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation.
(c) Radiation-chimeric strain 13 animals having F1 hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells.
Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells.
Two unexpected observations have been made in the course of this study: (a) F1 hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.