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T Germann

Publications and source records attributed to T Germann.

40 records · Page 3Linked to original sources

Involvement of soluble mediator(s) different from interleukin (IL) 1 in the antigen-induced IL 2 receptor expression and proliferation of L3T4+ (CD4+) T lymphocytes.

Proliferation of T lymphocytes (T cells) requires the interaction of interleukin 2 (IL 2) with the high affinity form of the IL 2 receptor (IL 2R). IL 2 production as well as IL 2R expression are generally induced simultaneously in T cells by the recognition of specific antigen displayed on the surface of syngeneic antigen-presenting cells. The experiments described herein show that the expression of IL 2R has different requirements than the production of IL 2 (and other lymphokines). Stimulation of antigen-specific L3T4+ T cell lines with antigen-pulsed spleen cells (SC) treated with ultraviolet (UV) light results in efficient IL 2 production but only minimal proliferation due to reduced IL 2R expression, as compared to T cells stimulated by antigen and SC without UV light treatment. The reduced IL 2R expression/proliferation correlates with the absence of a soluble mediator(s) termed T cell-stimulating factor (TSF) in the supernatants of T cells stimulated with antigen-pulsed, UV light-irradiated SC. Addition of TSF of these T cells could at least partially restore the proliferative response or enhance IL 2R expression. Because TSF is present in the supernatant of T cells triggered by antigen and SC but is absent when the latter are UV light treated, we suggest that TSF is a product of metabolically active splenic antigen-presenting cells. The macrophage products interleukin 1 alpha + beta as well as some other cytokines show no TSF activity.

Animals↗

An antigen-independent physiological activation pathway for L3T4+ T lymphocytes.

The data presented in this report describe an antigen-independent activation pathway leading to reinduction of proliferation of class II major histocompatibility complex (MHC)-restricted murine T cell lines that after previous antigen-specific stimulation reverted to a resting state. Antigen-independent proliferation and interleukin 2 (IL2)-receptor expression occur in the presence of splenic accessory cells, exogenous IL2 and a soluble factor(s) provisionally termed T cell-stimulating factor(s) (TSF). Each of these components is essential for inducing growth. TSF is found in the supernatant of an autoreactive T cell line upon stimulation with syngeneic accessory cells. Neither TSF nor accessory cells can be replaced by IL1 and by some other cytokines. Monoclonal antibodies against class II MHC molecules, the T cell receptor and L3T4 do not block this antigen-independent stimulation. This demonstrates that the function of the accessory cell in this system is not MHC restricted and that the T cell receptor is also not involved. Furthermore, it is suggested that the blocking of L3T4 molecules by antibody will mediate a negative signal only if T cells are triggered via their antigen receptors.

Animals↗

Co-development of naive CD4+ cells towards T helper type 1 or T helper type 2 cells induced by a combination of IL-12 and IL-4.

Cytokines were found to play a key role in Th cell differentiation. Among them IL-12 was shown to be a potent differentiation factor for Th1 cells, whereas IL-4 is the only known cytokine that promotes the development of Th2 cells. Upon addition of comparable amounts of IL-4 and IL-12 to a primary culture of naive CD4+ T cells activated by immobilized anti-CD3 mAb, it was found that the Th1-inducing capacity of IL-12 is dominated by the Th2-promoting effect of IL-4. However, high amounts of IL-12 (10,000 U/ml) in combination with low amounts of IL-4 (100 U/ml) led to the development of a Th cell population that, upon rechallenge, showed a substantial secondary IFN-gamma (Th1 cytokine) production concomitantly with the production of high amounts of IL-4 (Th2 cytokine). This can be due to the coexistence of Th1 and Th2 cells or to the development of Th0 cells producing a mixed pattern of cytokines. Immunofluorescence double staining of intracellular IL-4 and IFN-gamma in combination with flow cytometry (FACS) revealed that most of the emerging Th cells produced either IL-4 or IFN-gamma. Only a few double producers could be detected. This finding indicates that individual naive CD4+ T cells can differentiate under the same conditions towards Th1 or Th2 cells and implicates that the development of Th1 and Th2 cells is not necessarily mutually exclusive.

Animals↗