INDUCTION OF NK CELLS AND INTERMEDIATE TCR CELLS WITH PROTECTIVE ABILITY FROM VIRAL INFECTIOUS DEATH, AT THE EARLY PHASE OF HERPES-VIRUS INFECTION

Extrathymic T cells can be easily distinguished from thymus-derived T cells, in terms of their expression levels of TCR (or CD3) and IL-2 re ceptor beta-chain (IL-2R beta). In this study, we examined how extrath ymic T cells and thymus-derived T cells were activated in various orga ns during viral infection. When C3H/He mice were intraperitoneally ino culated with herpes simplex virus (HSV) of type 1-GC(+) strain at a su blethal dose, 3 x 10(4) PFU/mouse, the number of mononuclear cells (MN C) in the liver and spleen was stable but that of thymocytes decreased gradually up to 7 days after infection. However; a striking change of lymphocyte subsets was seen in the liver, namely, an increase in the proportion of NK cells (CD3-IL-2R beta(+)) and extrathymic T cells (CD 3-intermediate(+) IL-2R beta(+)) on day 3 and 7. Reflecting this chang e, gamma delta T cells and double-negative CD4(-)8(-) T cells, which a re components of extrathymic T cells, became elevated on day 3. Pre-el imination of NK cells and intermediate CD3 cells by an in vivo injecti on of anti-IL-2R beta mAb made mice susceptible to death by infection. All irradiated (6Gy) mice also became susceptible to death, but 1 X 1 0(7) adoptive transfer of Liver MNC, but not of splenic MNC, obtained from HSV-immunized mice was effective in preventing death (50%). The e xperiment in which mice were treated with anti-asialoGM, antibody show ed that NK cells were much more important for early phase protection t han were intermediate CD3 cells. MNC were also isolated from the lung, the major target organ, in HSV-infected mice. Intermediate CD3 cells and granulocytes increased in this organ. These results suggest that a serial induction of primitive lymphocytes such as NK cells and extrat hymic T cells may be crucial for early protection from viral infection .