CD4+CD8- thymocytes from neonatal mice induce IgM production in SCID mice.
Defective recombination of both the TCR and Ig genes results in the absence of mature lymphocytes in mice with the scid mutation. We have shown previously that the transfer of neonatal, but not adult, thymocytes results in high levels of Ig production in 100% of C.B-17-scid (SCID) mice, in contrast to the 10 to 25% of SCID mice spontaneously producing low levels of oligoclonal Ig. In this report we demonstrate that neonatal CD4+8- thymocytes were able to induce this response; the CD4+8+ and CD4-8+ subpopulations were totally inactive and CD4-8- T cells had only limited activity several weeks after transfer. The stimulation of IgM production in SCID mice was detectable by 1 wk posttransfer of CD4+8- thymocytes or splenic T cells, and could be achieved with as few as 300 cells. The ability of neonatal CD4+8- thymocytes to induce Ig diminished gradually to insignificant levels at 3 wk postbirth; this loss of function was not associated with differential survival of neonatal T cells. Neonatal CD4+8- thymocytes from C.B-17 and other H-2d strains rescued Ig production, whereas cells from H-2b, H-2a, and H-2k strains were much less effective. These results suggest that a CD4+8- subpopulation found in both neonatal thymus and peripheral lymphoid tissues is able to induce the expansion or differentiation of the small numbers of functional B lymphocytes in SCID mice, and that the inducing T cell disappears shortly after birth, perhaps during the acquisition of self-tolerance.
Riggs
J E
JE
Division of Immunology, Medical Biology Institute, La Jolla, CA 92037.
Hobbs
M V
MV
Mosier
D E
DE
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D007075:Immunoglobulin M / Q000096:biosynthesis*; D016219:Immunotherapy, Adoptive; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D007075:Immunoglobulin M