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The Shift of Th1 to Th2 Immunodominance Associated with the Chronicity of Mycobacterium bovis Bacille Calmette-Guérin Infection Does Not Affect the Memory Response ¹

Xinan Jiao^1,*,, Richard Lo-Man^*, Nathalie Winter, Edith Dériaud^*, Brigitte Gicquel and Claude Leclerc^2,*

^* Unité de Biologie des Régulations Immunitaires and Laboratoire du BCG, Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; and College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu, China.

In the present study we investigated the shaping and evolution of the immunodominance of the T cell response during a chronic mycobacterial infection. Using a recombinant bacille Calmette-Guérin expressing a reporter Ag, the Escherichia coli MalE protein, we analyzed the peptide specificity and the cytokine profile of the T cell response to the reporter Ag by ELISPOT. During the early steps of infection, the T cell response was focused on two dominant MalE epitopes and was characterized by a pure IFN- response. Then, in the course of infection the initial IFN- response to these two epitopes shifted to a mixed IFN-/IL-4 response. At the same time, the peptide specificity of the T cell response was broadened to two additional MalE epitopes characterized by a unique IL-4 response resulting in the establishment of a dominant IL-4 response to the MalE protein at 16 wk postinfection. However, this phenomenon did not impair the outcome of a predominant IFN- response upon subsequent MalE recall in vivo performed in the presence of CFA, a Th1-driving adjuvant. These results indicate that the Th2 nature of the immune response established during a chronic infection, which most likely reflects regulatory mechanisms to allow the return to T cell homeostasis, does not shape the Th1/Th2 nature of the memory response.

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