Characterization of murine newborn inhibitory T lymphocytes: functional and phenotypic comparison with an adult T cell subset activated in vitro by alphafetoprotein

Inhibitory T lymphocytes isolated from the spleens of newborn CBA/J mice which have high intrinsic levels of alpha‐fetoprotein (AFP) were compared, in terms of surface antigen phenotype and mode of immunosuppressive action, with a population of adult spleen T cells activated in vitro by a 4‐day preculture in the presence of purified AFP. The suppressing ability of these two groups of T cells was assayed on in vitro antibody synthesis of adult spleen cells to the T‐dependent (TD) and T independent (TI) antigens, sheep red blood cells and 2,4‐dinitrophenylated Ficoll. Negative selection of T cell subpopulations with antisera and complement showed that the inhibitory activity of newborn and adult AFP‐activated T cells on anti‐sheep red blood cell responses was abrogated by anti‐Thy‐1 anti‐Lyt 1, and by anti‐Ia^k (A. TH anti‐A. TL), whereas anti‐Lyt 2 antiserum and complement had no effect. Cytotoxic pretreatment with a panel of alloantisera specific for distinct products of major histocompatibility complex I subregions indicated that the Ia antigens expressed on the inhibitory T cells included I‐J, but not I‐EC determinants. Newborn and adult AFP‐activated inhibitory T cells could thus be shown to belong to a very similar, if not identical, subset of T lymphocytes characterized by the Thy‐1⁺, Lyt‐1⁺2⁻, I‐J⁺ phenotype. Both groups of T lymphocytes were shown to behave like efficient suppressor inducer cells in that they augmented TD antibody responses when added to purified B cell cultures which could not respond to TD antigen on their own, but caused strong inhibition of these responses when normal T cells were present. Dilution analyses of the two groups of inhibitory T cells showed that efficient suppressive activity was highly selective for TD responses, compared with a relatively weak inhibitory effect on TI responses. Passive administration of anti‐I‐J alloantibodies into newborn animals resulted in a significantly increased ability to respond to TD antigen, suggesting an anti‐I‐J‐mediated disruptive effect on newborn suppressor mechanisms. Our findings, therefore, indicate that TD antibody responses in newborn mice are regulated by an I‐J⁺ T cell‐mediated feedback inhibition circuit. Based on functional and phenotypic analyses, our results further suggest the probable identity of the naturally occurring inhibitory T cells in newborn mice and a subset of adult spleen T cells activated in vitro by AFP. This supports the contention that AFP may function as an important immunoregulatory agent in vivo.